Osteocytes Acidify Their Microenvironment in Response to PTHrP In Vitro and in Lactating Mice In Vivo
Open accessAbstract
Osteocytes appear to mobilize calcium within minutes in response to PTH injections; we have previously shown that osteocytes remove their perilacunar matrix during lactation through activation of the PTH type 1 receptor. Mechanisms utilized by osteocytes to mobilize calcium are unknown but we hypothesized that the molecular components may be similar to those used by osteoclasts. Here we show, using IDG-SW3 cells that ATP6V0D2, an essential component of vacuolar ATPase in osteoclasts, and other genes associated with osteoclastic bone resorption, increase with osteoblast to osteocyte differentiation. Furthermore, PTHrP increases ATP6V0D2 expression and induces proton generation by primary osteocytes, which is blocked by bafilomycin, a vacuolar ATPase inhibitor. These in vitro proton measurements raised the question of osteocyte viability in an acidic environment. Interestingly, osteocytes, showed enhanced viability at pH as low as 5 compared to osteoblasts and fibroblasts in vitro. To study in vivo acidification by osteocytes, virgin and lactating CD1 mice on a low calcium diet were injected with the pH indicator dye, acridine orange, and their osteocyte lacuno-canalicular system imaged by confocal microscopy. Lower pH was observed in lactating compared to virgin animals. In addition, a novel transgenic mouse line with a topaz variant of green fluorescent protein (GFPtpz)-tagged collagen α2(I) chain was used. Instead of the expected reduction in GFP-fluorescence only in the perilacunar matrix, reduced fluorescence was observed in the entire bone matrix of lactating mice. Based on our experiments showing quenching of GFP in vitro, we propose that the observed reduction in GFP fluorescence in lactating mice is due to quenching of GFP by the acidic pH generated by osteocytes. Together these findings provide novel mechanistic insight into how osteocytes remove calcium from their perilacunar/pericanalicular matrices through active acidification of their microenvironment and show that osteocytes, like osteoclasts, are resistant to the negative effects of acid on viability. © 2017 American Society for Bone and Mineral Research.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Magenta cluster genes may be important in regulation of perilacunar-resorption.
“Together this suggests the Magenta cluster genes may be important in regulation of perilacunar-resorption15,37.”
From Osteocyte transcriptome mapping identifies a molecular landscape controlling skeletal homeostasis and susceptibility to skeletal disease (2021) · cites this paper as [37]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Bonewald, L. F. (2011) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.320 · Cited by 2,287 · cited 4× · see citing works
“Address correspondence to: Lynda F Bonewald, PhD, Indiana University, Indiana Center for Musculoskeletal Health, 635 Barnhill Dr., Indianapolis, IN 46202, USA.”
BackgroundInfluentialSelf-citationThe Osteocyte: An Endocrine Cell … and More
Dallas, S. L., Prideaux, M., & Bonewald, L. F. (2013) · Endocrine Reviews · doi:10.1210/er.2012-1026 · Cited by 1,042 · cited 2× · see citing works
“Osteocytes have been attributed with multiple roles ranging from mechanosensation to endocrine functions including regulating kidney function, hematopoiesis, and fat metabolism to name a few (for review see Dallas and colleagues((3))).”
BackgroundSelf-citationMicroelectrode studies on the acid microenvironment beneath adherent macrophages and osteoclasts*1
Silver, I. A. (1988) · Experimental Cell Research · doi:10.1016/0014-4827(88)90191-7 · Cited by 903 · cited 1× · see citing works
“7 depending on the experimental setup for determination.((28)) Here we estimated osteocyte-mediated acidification to generate a theoretical proton concentration of 6.”
BackgroundOsteoclastic Bone Resorption by a Polarized Vacuolar Proton Pump
Blair, H. C., Teitelbaum, S. L., Ghiselli, R. W., & Gluck, S. L. (1989) · Science · doi:10.1126/science.2528207 · Cited by 862 · cited 2× · see citing works
“The hydroxyapatite of bone is demineralized by osteoclasts via acidification, whereby protons are generated intracellularly by carbonic anhydrases and transported into the sealed zone via the action of proton pumps; ie, vacuolar ATPases.”
BackgroundBurgess, A., Vigneron, S., Brioudes, E., Labbé, J., Lorca, T., & Castro, A. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0914191107 · Cited by 681 · cited 6× · see citing works
“Corrected total GFP fluorescence/area (CTCF)(16) was calculated as CTCF¼ integrated density – (standardized area mean background fluorescence).”
MethodInfluentialEstablishment of an Osteocyte-like Cell Line, MLO-Y4
Kato, Y., Windle, J. J., Koop, B. A., Mundy, G. R., & Bonewald, L. F. (1997) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.1997.12.12.2014 · Cited by 549 · cited 1× · see citing works
“MLO-Y4 cells (used at passages 20 to 40) and MLO-A5 cells were cultured as described((10,11)) with a-MEMþ P/Sþ 2.”
MethodSelf-citationDemonstration of osteocytic perilacunar/canalicular remodeling in mice during lactation
Qing, H., Ardeshirpour, L., Divieti Pajevic, P., Dusevich, V., Jähn, K., Kato, S., Wysolmerski, J., & Bonewald, L. F. (2012) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.1567 · Cited by 489 · cited 10× · see citing works
“We and others have recently demonstrated that osteocytes are capable of expressing so called “osteoclast-specific” bone resorption marker genes both at the mRNAand theprotein level.((6,25,26)) Interestingly, osteocytesexpress”
BackgroundMethodInfluentialSelf-citationThe Death of Osteocytes via Apoptosis Accompanies Estrogen Withdrawal in Human Bone
Tomkinson, A., REEVE, J., Shaw, R. W., & Noble, B. (1997) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.82.9.4200 · Cited by 417 · cited 1× · see citing works
“whether drug-induced or due to aging, is a hallmark of bone fragility and development of osteoporosis.((32,33)) It appears that osteocytes possess a high survival potential, as demonstrated by the role of the survival mechanism autophagy in these cells, whereby osteocytes seem to have a large intrinsic capacity to wit…”
BackgroundApoptosis of Osteocytes in Glucocorticoid-Induced Osteonecrosis of the Hip 1
Weinstein, R. S., Nicholas, R. W., & Manolagas, S. C. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.8.6714 · Cited by 397 · cited 1× · see citing works
“whether drug-induced or due to aging, is a hallmark of bone fragility and development of osteoporosis.((32,33)) It appears that osteocytes possess a high survival potential, as demonstrated by the role of the survival mechanism autophagy in these cells, whereby osteocytes seem to have a large intrinsic capacity to wit…”
BackgroundArchitecture of the osteocyte network correlates with bone material quality
Kerschnitzki, M., Kollmannsberger, P., Burghammer, M. C., Duda, G. N., Weinkamer, R., Wagermaier, W., & Fratzl, P. (2013) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.1927 · Cited by 361 · cited 1× · see citing works
“Kerschnitzki and colleagues((38)) have shown that each canaliculi is nomore than 1mm apart in the bone, suggesting the potential for significant penetration of the acidified bone fluid throughout the bone matrix.”
BackgroundInaoka, T., Bilbe, G., Ishibashi, O., Tezuka, K., Kumegawa, M., & Kokubo, T. (1995) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1995.1013 · Cited by 352 · cited 1× · see citing works
“The organic matrix components of bone are digested by proteases such as cathepsin K.((8)) We hypothesized that osteocytes must be able to acidify their microenvironment to remove calcium from their perilacunar matrix, and that the molecular mechanisms mediating this would be similar to those used in osteoclastic bone…”
BackgroundApoptosis of Osteocytes in Glucocorticoid-Induced Osteonecrosis of the Hip
Weinstein, R. S. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.85.8.2907 · Cited by 315 · see citing works
Woo, S. M., Rosser, J., Dusevich, V., Kalajzic, I., & Bonewald, L. F. (2011) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.465 · Cited by 243 · cited 1× · see citing works
“IDG-SW3 are immortalized cells that have been previously established as a suitable in vitro model for osteoblast-toosteocyte differentiation.((9)) Cells were cultured on type I collagen–coated plates and dishes (rat tail type I collagen; BD Biosciences, San Jose, CA, USA) at passages 7 to 25 and seeded at 40,000 cells…”
MethodSelf-citationTang, S. Y., Herber, R., Ho, S. P., & Alliston, T. N. (2012) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.1646 · Cited by 228 · cited 1× · see citing works
“Tang and colleagues((36)) used a mouse model with a global deletion of the matrix metalloproteinase-13 (MMP13) to demonstrate that osteocytic perilacunar remodeling with lactation is impaired in the absence of MMP13.”
BackgroundKalajzić, I., Braut, A., Guo, D., Jiang, X., Kronenberg, M. S., Mina, M., Harris, M. A., Harris, S. E., & Rowe, D. W. (2004) · Bone · doi:10.1016/j.bone.2004.03.006 · Cited by 220 · cited 1× · see citing works
“David Rowe, University of Connecticut Health Center) and expressing green fluorescent protein (GFP) driven by an 8-kb Dmp1-promoter fragment.((13)) Four serial digests with collagenase/trypsin solution (0.”
BackgroundOverly, C. C., Lee, K. D., Berthiaume, E. P., & Hollenbeck, P. J. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.8.3156 · Cited by 217 · cited 1× · see citing works
“The ratio of red channel CTCF/green channel CTCF was determined.((17))”
BackgroundIn situ measurement of solute transport in the bone lacunar-canalicular system
Wang, L., Wang, Y., Han, Y., Henderson, S. C., Majeska, R. J., Weinbaum, S., & Schaffler, M. B. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0505193102 · Cited by 214 · cited 1× · see citing works
“Assuming an estimated lacuno-canalicular fluid volume (estimations based on unpublished data and((20,21))) of 100mm(3) (ie, 10 L) this would equate to a molar concentration of Hþ ions in the lacuno-canalicular fluid of 6.”
Isolation and Culture of Primary Osteocytes from the Long Bones of Skeletally Mature and Aged Mice
Stern, A. R., Stern, M. M., Dyke, M. E. V., Jähn, K., Prideaux, M., & Bonewald, L. F. (2012) · BioTechniques · doi:10.2144/0000113876 · Cited by 207 · cited 1× · see citing works
“Primary long bone–derived cells enriched for fibroblasts, osteoblasts, or osteocytes were isolated from adult C57Bl/6mice as described.((12)) Serial digestions with collagenase IA from Clostridium histolyticum and ethylenediaminetetraacetic acid (EDTA) solution (Sigma-Aldrich) were done.”
MethodSelf-citationEstablishment of an Osteoid Preosteocyte-like Cell MLO-A5 That Spontaneously Mineralizes in Culture
Kato, Y., Boskey, A. L., Spevak, L., Dallas, M., Hori, M., & Bonewald, L. F. (2001) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2001.16.9.1622 · Cited by 207 · cited 1× · see citing works
“MLO-Y4 cells (used at passages 20 to 40) and MLO-A5 cells were cultured as described((10,11)) with a-MEMþ P/Sþ 2.”
MethodSelf-citationSuppression of Autophagy in Osteocytes Mimics Skeletal Aging
Onal, M., Piemontese, M., Xiong, J., Wang, Y., Han, L., Ye, S., Komatsu, M., Selig, M., Weinstein, R. S., Zhao, H., et al. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.444190 · Cited by 206 · cited 1× · see citing works
“It appears that osteocytes possess a high survival potential, as demonstrated by the role of the survival mechanism autophagy in these cells, whereby osteocytes seem to have a large intrinsic capacity to withstand external stress situations.((34,35)) Recently, studies have provided more insight into how perilacunar ma…”
BackgroundSelf-citationOsteocytes: The master cells in bone remodelling
Prideaux, M., Findlay, D. M., & Atkins, G. J. (2016) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2016.02.003 · Cited by 205 · cited 1× · see citing works
“Osteocytes regulate the activity of osteoclasts through the expression of osteoprotegerin and receptor activator of nuclear factor k-B ligand (RANKL) and negatively regulate osteoblasts through the expression of sclerostin (reviewed in Prideaux and colleagues,((1)) Bonewald,((2)) and Dallas and colleagues((3))).”
BackgroundPowell, W. F., Barry, K. J., Tulum, I., Kobayashi, T., Harris, S. E., Bringhurst, F. R., & Pajevic, P. D. (2011) · Journal of Endocrinology · doi:10.1530/joe-10-0308 · Cited by 202 · cited 1× · see citing works
“Mice lacking this receptor specifically in osteocytes have impaired calcium homeostasis when subjected to a low calcium diet and do not respond to secondary hyperparathyroidism.((24)) It has also been shown that these samemice fail to remodel their perilacunar matrix with lactation.”
BackgroundKitase, Y., Barragan, L., Qing, H., Kondoh, S., Jiang, J. X., Johnson, M. L., & Bonewald, L. F. (2010) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.168 · Cited by 199 · cited 1× · see citing works
“The percentage of live cells was quantified using the trypan blue exclusion method following published procedures.((14)) Briefly,”
MethodSelf-citationOsteocytic Canalicular Networks: Morphological Implications for Altered Mechanosensitivity
Milovanovic, P. D., Zimmermann, E. A., Hahn, M. P., Djonić, D., Püschel, K., Djuric, M. P., Amling, M., & Busse, B. (2013) · ACS Nano · doi:10.1021/nn401360u · Cited by 186 · cited 1× · see citing works
“Lying within the fluid-filled lacuno-canalicular space, the global osteocyte network spans throughout the entire bone matrix, governing a large surface area and connecting to neighboring cells, surface cells, and blood vessels to allow for communication and solute transport.((4))”
BackgroundTowards quantitative 3D imaging of the osteocyte lacuno-canalicular network
Schneider, P., Meier, M., Wepf, R. A., & Müller, R. (2010) · Bone · doi:10.1016/j.bone.2010.07.026 · Cited by 174 · see citing works
Glucocorticoid dose determines osteocyte cell fate
Jia, J., Yao, W., Guan, M., Dai, W., Shahnazari, M., Kar, R., Bonewald, L., Jiang, J. X., & Lane, N. E. (2011) · The FASEB Journal · doi:10.1096/fj.11-182519 · Cited by 157 · cited 1× · see citing works
“It appears that osteocytes possess a high survival potential, as demonstrated by the role of the survival mechanism autophagy in these cells, whereby osteocytes seem to have a large intrinsic capacity to withstand external stress situations.((34,35)) Recently, studies have provided more insight into how perilacunar ma…”
BackgroundSelf-citationSclerostin Regulates Release of Bone Mineral by Osteocytes by Induction of Carbonic Anhydrase 2
Kogawa, M., Wijenayaka, A. R., Ormsby, R. T., Thomas, G. P., Anderson, P., Bonewald, L. F., Findlay, D. M., & Atkins, G. J. (2013) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.2003 · Cited by 153 · cited 1× · see citing works
“Thishasbeensuggestedby the work from Kogawa and colleagues((27)) demonstrating sclerostin regulation of carbonic anhydrase 2, an enzyme needed for proton generation, in osteocytic cells in vitro.”
BackgroundSelf-citationWu, H., Xu, G., & Li, Y. (2008) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.081239 · Cited by 145 · cited 1× · see citing works
“ATP6V0D2 is an isoform of the d subunit in the vacuolar ATPase and has been shown to be an essential component of the proton pump that mediates extracellular acidification in osteoclast-dependent bone resorption.((18)) PTHrP-induced acidification by osteocytes in vitro involves vacuolar ATPase”
BackgroundNovel approaches for two and three dimensional multiplexed imaging of osteocytes
Kamel-ElSayed, S. A., Tiede-Lewis, L. M., Lu, Y., Veno, P. A., & Dallas, S. L. (2015) · Bone · doi:10.1016/j.bone.2015.02.011 · Cited by 87 · cited 3× · see citing works
“We had proposed to investigate osteocyte perilacunar turnover of bone matrix proteins in vivo utilizing a novel transgenic mouse model where the ɑ2 chain of type I collagen was tagged with GFPtpz, because GFP fluorescence is observed around the osteocyte lacunae with fainter GFP expression throughout the matrix((15))…”
BackgroundMethodInfluentialSelf-citationHuman osteoblasts produce cathepsin K
Mandelin, J., Hukkanen, M., Li, T.-F., Korhonen, M. O., Liljeström, M., Sillat, T., Hanemaaijer, R., Salo, J., Santavirta, S. S., & Konttinen, Y. T. (2005) · Bone · doi:10.1016/j.bone.2005.10.017 · Cited by 73 · see citing works
The Effect of pH on Green Fluorescent Protein: a Brief Review
Campbell, T. R. (2001) · Cited by 63 · see citing works
Ardeshirpour, L., Brian, S. R., Dann, P. R., VanHouten, J. N., & Wysolmerski, J. J. (2010) · Endocrinology · doi:10.1210/en.2010-0566 · Cited by 61 · see citing works
The role of osteocytes in bone regulation: mineral homeostasis versus mechanoreception.
Cullinane, D. M. (2002) · PubMed · Cited by 58 · see citing works
Clarke, M. V., Russell, P. K., Findlay, D. M., Sastra, S., Anderson, P. H., Skinner, J. P., Atkins, G. J., Zajac, J. D., & Davey, R. A. (2015) · Endocrinology · doi:10.1210/en.2015-1345 · Cited by 54 · cited 1× · see citing works
“Also, a role for the calcitonin receptor on osteocytes, potentially antagonizing the PTH1R, was suggested to play a role in lactation-induced osteocytic osteolysis.((37)) Here, we utilized twomodel systems to determine in vivo acidification by osteocytes.”
MethodTalmage, R. V., Doppelt, S. H., & Fondren, F. B. (1977) · Calcified Tissue International · doi:10.1007/bf02010351 · Cited by 51 · cited 1× · see citing works
“osteolysis seems to be inducible early during lactation ensuring initial calcium supply.((31)) Moreover, in comparison to fibroblasts and even osteoblasts, osteocytes demonstrated increased survival rates at low pH.”
BackgroundSano, H., Kikuta, J., Furuya, M., Kondo, N., Endo, N., & Ishii, M. (2015) · Bone · doi:10.1016/j.bone.2015.01.013 · Cited by 50 · cited 1× · see citing works
“An estimation of osteocyte-dependent acidification has been recently made by the group of Sano and colleagues,((29)) suggesting that osteocytic osteolysis occurs around pH1⁄4 5.”
MethodNakano, Y., Toyosawa, S., & Takano, Y. (2004) · Journal of Histochemistry & Cytochemistry · doi:10.1369/jhc.4a6378.2004 · Cited by 47 · cited 1× · see citing works
“We and others have recently demonstrated that osteocytes are capable of expressing so called “osteoclast-specific” bone resorption marker genes both at the mRNAand theprotein level.((6,25,26)) Interestingly, osteocytesexpress”
BackgroundA New Action of Parathyroid Hormone
Barrett, M. G., Belinsky, G. S., & Tashjian, A. H. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.42.26346 · Cited by 30 · cited 1× · see citing works
“Previously, SaOs2 cells were shown to acidify their culture medium upon PTH treatment.((19)) Here, for a negative control, NIH3T3 fibroblasts were used and SaOs2 osteosarcoma cells were used as a positive control for comparison to IDG-SW3 cells and primary longbone–derived osteocytes.”
Method
Flagged first, then by citations
1 of the 39 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Robling, A. G., & Bonewald, L. F. (2020) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021119-034332 · Cited by 539 · see citing works
“PTHrP, which is highly elevated during lactation, was shown to induce a decrease in osteocyte extracellular pH in vitro, and in vivo lactating mice showed a decreased pH within their osteocyte network (44).”
BackgroundThe role of osteoblasts in energy homeostasis
Dirckx, N., Moorer, M. C., Clemens, T. L., & Riddle, R. C. (2019) · Nature Reviews Endocrinology · doi:10.1038/s41574-019-0246-y · Cited by 292 · see citing works
Regulation of Bone Remodeling by Parathyroid HormonePreprint
Wein, M. N., & Kronenberg, H. M. (2018) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a031237 · Cited by 243 · see citing works
“Indeed, lactating calcium-deficient mice show reduced perilacunar pH, as assessed using a novel green fluorescent protein (GFP)-based reporter system (Jahn et al. 2017).”
BackgroundDegeneration of the osteocyte network in the C57BL/6 mouse model of aging
Tiede-Lewis, L. M., Xie, Y., Hulbert, M. A., Campos, R., Dallas, M. R., Dusevich, V., Bonewald, L. F., & Dallas, S. L. (2017) · Aging · doi:10.18632/aging.101308 · Cited by 176 · see citing works
“This is achieved through the expression of genes related to osteoclastic resorption (but not differentiation), such as TRAP, cathepsin K and vacuolar proton pump subunits, ATP6V0D2 and ATP6V1G1, as well as matrix metalloproteinases 13 and 14 [40-42].”
Self-citationYoulten, S. E., Kemp, J. P., Logan, J. G., Ghirardello, E. J., Sergio, C. M., Dack, M. R. G., Guilfoyle, S. E., Leitch, V. D., Butterfield, N. C., Komla-Ebri, D., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-22517-1 · Cited by 133 · see citing works
The Mechanosensory Role of Osteocytes and Implications for Bone Health and Disease States
Choi, J. U. A., Kijas, A. W., Lauko, J., & Rowan, A. E. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.770143 · Cited by 127 · see citing works
Changes in the osteocyte lacunocanalicular network with aging
Tiede-Lewis, L. M., & Dallas, S. L. (2019) · Bone · doi:10.1016/j.bone.2019.01.025 · Cited by 122 · see citing works
Self-citationPhysiological and pathological osteocytic osteolysis.
Tsourdi, E. A., Jähn, K., Rauner, M., Busse, B., & Bonewald, L. F. (2018) · Europe PMC (PubMed Central) · Cited by 109 · see citing works
Self-citationThe role of biomineralization in disorders of skeletal development and tooth formation
Kovács, C. S., Chaussain, C., Osdoby, P., Brandi, M. L., Clarke, B. L., & Thakker, R. V. (2021) · Nature Reviews Endocrinology · doi:10.1038/s41574-021-00488-z · Cited by 109 · see citing works
Bone Metastasis Pain, from the Bench to the Bedside
Aielli, F., Ponzetti, M., & Rucci, N. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20020280 · Cited by 90 · see citing works
“This can happen directly, through cancer cells expression of RANKL (most common) or by exploiting osteoblasts and/or osteocytes, which are stimulated to produce RANKL through cancer-cell-released PTHrP [55] and in the case of osteocytes, to resorb bone directly [4,56].”
BackgroundLotinun, S., Ishihara, Y., Nagano, K., Kiviranta, R., Carpentier, V. T., Neff, L., Parkman, V.-J. A., Ide, N., Hu, D. Z., Dann, P. R., et al. (2019) · Journal of Clinical Investigation · doi:10.1172/jci122936 · Cited by 80 · see citing works
Solute Transport in the Bone Lacunar-Canalicular System (LCS)
Wang, L. (2018) · Current Osteoporosis Reports · doi:10.1007/s11914-018-0414-3 · Cited by 80 · see citing works
Rolvien, T., Milovanovic, P. D., Schmidt, F. N., Kroge, S. V., Wölfel, E. M., Krause, M., Wulff, B., Püschel, K., Ritchie, R. O., Amling, M., et al. (2020) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.3970 · Cited by 76 · see citing works
“…that in this condition lacunar remodeling is suppressed to a minimum level since there is no need for additional calcium removal around the osteocyte lacunae as opposed to, for example, lactation (52) or vitamin D de fi ciency, (30,53) both conditions in which osteocyte lacunar areas are increased.”
BackgroundVitamin D regulates osteocyte survival and perilacunar remodeling in human and murine bone
Rolvien, T., Krause, M., Jeschke, A., Yorgan, T., Püschel, K., Schinke, T., Busse, B., Demay, M. B., & Amling, M. (2017) · Bone · doi:10.1016/j.bone.2017.06.022 · Cited by 74 · see citing works
“An increase in osteocyte lacunar size and pericanalicular remodeling is also seen in lactating mice [21,36], suggesting that maintaining normocalcemia occurs at the expense of skeletal integrity in hypocalcemic Vdr-deficient mice and during lactation [37].”
BackgroundEnergy metabolism: A newly emerging target of BMP signaling in bone homeostasis
Yang, J., Ueharu, H., & Mishina, Y. M. (2020) · Bone · doi:10.1016/j.bone.2020.115467 · Cited by 74 · see citing works
Reznikov, N., Hoac, B., Buss, D. J., Addison, W. N., Barros, N. M. T., & McKee, M. D. (2020) · Bone · doi:10.1016/j.bone.2020.115447 · Cited by 69 · see citing works
Investigating Osteocytic Perilacunar/Canalicular Remodeling
Yee, C. S., Schurman, C. A., White, C. R., & Alliston, T. N. (2019) · Current Osteoporosis Reports · doi:10.1007/s11914-019-00514-0 · Cited by 71 · see citing works
Control of Bone Matrix Properties by Osteocytes
Creecy, A., Damrath, J. G., & Wallace, J. M. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.578477 · Cited by 68 · see citing works
“Studies using IDG-SW3 cells have demonstrated that PTH upregulates ATPase H+ Transporting V0 Subunit D2 (ATP6V0D2), a proton pump on the cell membrane that acidifies the extracellular environment, indicating that osteocytes can acidify their extracellular environment to degrade mineral (74).”
BackgroundParathyroid Hormone Signaling in Osteocytes
Wein, M. N. (2017) · JBMR Plus · doi:10.1002/jbm4.10021 · Cited by 64 · see citing works
“Indeed, lactating calcium-deficient mice show reduced perilacunar pH, as assessed using a novel GFP-based reporter system.((104)) PTH/PTHrP-dependent regulation of perilacunar pH may represent a rapid mechanism for osteocytes to liberate readily accessible pools of calcium.”
The osteocyte and its osteoclastogenic potential
Marahleh, A., Kitaura, H., Ohori, F., Noguchi, T., & Mizoguchi, I. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1121727 · Cited by 53 · see citing works
“Lactation and rapid release of calcium Parathyroid hormonerelated peptide (PTHrP) Release of Cathepsin K (CTSK), tartrate acid phosphatase (Acp5), Matrix metalloproteinase 13 (MMP13), carbonic anhydrase 1, 2, and vacuole ATPase components Induces osteocytic perilacunar remolding (84, 85)”
BackgroundMotyl, K. J., Guntur, A. R., Carvalho, A., & Rosen, C. J. (2017) · Toxicologic Pathology · doi:10.1177/0192623317737065 · Cited by 50 · see citing works
“These cells have been shown to generate protons and acidify their microenvironment (Jahn et al. 2017), though there are currently no published studies that have examined energy metabolism in osteocytes.”
BackgroundRegulatory mechanisms and clinical manifestations of musculoskeletal aging
Grote, C. W., Reinhardt, D., Zhang, M., & Wang, J. (2019) · Journal of Orthopaedic Research® · doi:10.1002/jor.24292 · Cited by 53 · see citing works
“, estrogen and parathyroid hormone) on osteoblasts, osteoclasts, and osteocyte activities, alterations in cellular response to hormones, and vitamin D metabolism.(118,119) These changes may increase intra-cortical porosity through remodeling and coalescence of existing cortical canals.”
BackgroundLacunar-canalicular bone remodeling: Impacts on bone quality and tools for assessment
Vahidi, G., Rux, C. J., Sherk, V. D., & Heveran, C. M. (2020) · Bone · doi:10.1016/j.bone.2020.115663 · Cited by 46 · see citing works
The contribution of the pericanalicular matrix to mineral content in human osteonal bone
Roschger, A., Roschger, P., Wagermaier, W., Chen, J., van Tol, A. F., Repp, F., Blouin, S., Berzlanovich, A. M., Gruber, G. M., Klaushofer, K., et al. (2019) · Bone · doi:10.1016/j.bone.2019.03.018 · Cited by 45 · see citing works
“This is in line with reports that osteocytes express markers that are usually attributed to osteoclasts’ resorption activities like cathepsin K or tartrate-resistant acid phosphatase (TRAP) (22) .”
BackgroundBailey, K. N., Nguyen, J., Yee, C. S., Dole, N. S., Dang, A. C., & Alliston, T. N. (2020) · Arthritis & Rheumatology · doi:10.1002/art.41548 · Cited by 44 · see citing works
Tunnels in the rock: Dynamics of osteocyte morphogenesis
Moharrer, Y., & Boerckel, J. D. (2021) · Bone · doi:10.1016/j.bone.2021.116104 · Cited by 43 · see citing works
Hashimoto, R., Minoshima, M., Kikuta, J., Yari, S., Bull, S. D., Ishii, M., & Kikuchi, K. (2020) · Angewandte Chemie International Edition · doi:10.1002/anie.202006388 · Cited by 41 · see citing works
Bone metabolism and evolutionary origin of osteocytes: Novel application of FIB-SEM tomography
Haridy, Y., Osenberg, M., Hilger, A., Manke, I., Davesne, D., & Witzmann, F. (2021) · Science Advances · doi:10.1126/sciadv.abb9113 · Cited by 39 · see citing works
Metabolic Health and Disease: A Role of Osteokines?
Shimonty, A., Bonewald, L. F., & Huot, J. R. (2023) · Calcified Tissue International · doi:10.1007/s00223-023-01093-0 · Cited by 38 · see citing works
“During lactation, PTHrP facilitates osteocytes to increase RANKL and activate osteoclastic bone resorption as well as osteocytic osteolysis to release calcium [105].”
BackgroundSelf-citationTGFβ Regulation of Perilacunar/Canalicular Remodeling Is Sexually Dimorphic
Dole, N. S., Yee, C. S., Mazur, C. M., Acevedo, C., & Alliston, T. N. (2020) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.4023 · Cited by 38 · see citing works
“PTH/PTHrP during lactation by inducing perilacunar/canalicular remodeling (PLR).((21,22)) In PLR, osteocytes resorb, and later”
BackgroundEnergy Metabolism of Osteocytes
Karthik, V., & Guntur, A. R. (2021) · Current Osteoporosis Reports · doi:10.1007/s11914-021-00688-6 · Cited by 36 · see citing works
Non-bone metastatic cancers promote osteocyte-induced bone destruction
Pin, F., Prideaux, M., Huot, J. R., Essex, A. L., Plotkin, L. I., Bonetto, A., & Bonewald, L. F. (2021) · Cancer Letters · doi:10.1016/j.canlet.2021.06.030 · Cited by 36 · see citing works
Self-citationAcid Microenvironment in Bone Sarcomas
Pompo, G. D., Cortini, M., Baldini, N., & Avnet, S. (2021) · Cancers · doi:10.3390/cancers13153848 · Cited by 34 · see citing works
“As with osteoclasts, this process relies on the combined activity of MMPs, vacuolar acid-secreting H+-ATPases [73,74], and other enzymes, such as cathepsin”
BackgroundCrosstalk within a brain-breast-bone axis regulates mineral and skeletal metabolism during lactation
Athonvarangkul, D., & Wysolmerski, J. J. (2023) · Frontiers in Physiology · doi:10.3389/fphys.2023.1121579 · Cited by 30 · see citing works
“Subsequent studies have shown that osteocytes upregulate proton pumps that allow them to acidify their microenvironment (Jähn et al., 2017) and they also secrete Cathepsin K and matrix metallopeptidase 13 (MMP13), which are required for enlargement of the lacunae (Tang et al.”
BackgroundA review of mathematical modeling of bone remodeling from a systems biology perspective
Cook, C. V., Lighty, A. M., Smith, B. J., & Ford Versypt, A. N. (2024) · Frontiers in Systems Biology · doi:10.3389/fsysb.2024.1368555 · Cited by 25 · see citing works
Sang, W., & Ural, A. (2023) · Current Osteoporosis Reports · doi:10.1007/s11914-023-00792-9 · Cited by 26 · see citing works
Mechanical Regulation of the Maternal Skeleton during Reproduction and Lactation
Liu, X. S., Wang, L., de Bakker, C. M. J., & Lai, X. (2019) · Current Osteoporosis Reports · doi:10.1007/s11914-019-00555-5 · Cited by 26 · see citing works
Lai, X., Chung, R., Li, Y., Liu, X. S., & Wang, L. (2021) · Bone · doi:10.1016/j.bone.2021.116033 · Cited by 26 · see citing works
Cell Sheet Technology as an Engineering-Based Approach to Bone Regeneration
You, Q., Lu, M., Li, Z., Zhou, Y., & Tu, C. (2022) · International Journal of Nanomedicine · doi:10.2147/ijn.s382115 · Cited by 26 · see citing works
“While this technique was effective as a means of facilitating cell sheet harvesting, it induced unavoidable cellular damage owing to the pHsensitive nature of cells.(92) Separation of cells in response to pH shifts was facilitated by Chen et al(93) using a novel chitosan-based method.”
MethodHemmatian, H., Thiele, S., Furesi, G., Mletzko, K., Krug, J., Failla, A. V., Kuhlmann, J. D., Rauner, M., Busse, B., & Jähn, K. (2021) · Bone · doi:10.1016/j.bone.2021.116074 · Cited by 25 · see citing works
Self-citationCooper, I. D., Brookler, K. H., & Crofts, C. A. P. (2021) · Biomedicines · doi:10.3390/biomedicines9091165 · Cited by 25 · see citing works
“These phases of life lend a physiological adaptive explanation as to why we would see an increase in BMD in T2DM hyperinsulinaemia [30,32,133].”
BackgroundDole, N. S., Yee, C. S., Schurman, C. A., Dallas, S. L., & Alliston, T. N. (2020) · Methods in molecular biology · doi:10.1007/978-1-0716-1028-2_17 · Cited by 24 · see citing works
Self-citationJandl, N. M., Kroge, S. V., Stürznickel, J., Baranowsky, A., Stockhausen, K. E., Mushumba, H., Beil, F. T., Püschel, K., Amling, M., & Rolvien, T. (2020) · Bone · doi:10.1016/j.bone.2020.115324 · Cited by 24 · see citing works
Bisphosphonate-incorporated coatings for orthopedic implants functionalization
Zhang, J., Bai, H., Bai, M., Wang, X., Li, Z., Xue, H., Wang, J., Cui, Y., Wang, H., Wang, Y., et al. (2023) · Materials Today Bio · doi:10.1016/j.mtbio.2023.100737 · Cited by 22 · see citing works
PINK1-mediated mitophagy contributes to glucocorticoid-induced cathepsin K production in osteocytes
Yuan, J., Gao, Y., Liu, D., Tai, A. C. P., Zhou, H., Papadimitriou, J. M., Zhang, C., Zheng, M., & Gao, J. (2022) · Journal of Orthopaedic Translation · doi:10.1016/j.jot.2022.11.003 · Cited by 21 · see citing works
“revealed that osteocytes can remove calcium in the perilacunar matrix by acidifying their microenvironment through v-ATPase during lactation [65].”
BackgroundSwitching Homes: How Cancer Moves to Bone
Ponzetti, M., & Rucci, N. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21114124 · Cited by 20 · see citing works
Jähn, K., & Zimmermann, E. A. (2021) · Current Osteoporosis Reports · doi:10.1007/s11914-021-00686-8 · Cited by 18 · see citing works
Self-citationDamrath, J. G., Moe, S. M., & Wallace, J. M. (2020) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.4574 · Cited by 18 · see citing works
“Further, PTH signaling is essential for perilacunar remodeling and has been shown to mediate extracellular acidification, an essential step in the removal of bone mineral in the perilacunar region.((20)) Therefore, it is plausible that the bone matrix near the osteocyte lacunae may present with differential compositio…”
BackgroundOsteocyte Remodeling of the Lacunar-Canalicular System: What’s in a Name?
Heveran, C. M., & Boerckel, J. D. (2022) · Current Osteoporosis Reports · doi:10.1007/s11914-022-00766-3 · Cited by 18 · see citing works
Li, Y., de Bakker, C. M. J., Lai, X., Zhao, H., Parajuli, A., Tseng, W., Pei, S., Tan, M., Chung, R., Wang, L., et al. (2021) · Bone · doi:10.1016/j.bone.2021.116031 · Cited by 18 · see citing works
Self-citationRole of the Osteocyte in Musculoskeletal Disease
Shimonty, A., Bonewald, L. F., & Pin, F. (2023) · Current Osteoporosis Reports · doi:10.1007/s11914-023-00788-5 · Cited by 16 · see citing works
“Recent years have seen an increase of interest in this osteocyte function, and studies are being performed to examine this function under both physiological conditions such as lactation [19, 20] and pathological conditions including hyperparathyroidism and hypophosphatemic rickets [16, 21].”
BackgroundSelf-citationVadivalagan, C., Krishnan, A., Chen, S.-J., Hseu, Y., Muthu, S., Dhar, R., Aljabali, A. A. A., & Tambuwala, M. M. (2022) · Cellular Signalling · doi:10.1016/j.cellsig.2022.110488 · Cited by 17 · see citing works
Kroge, S. V., Wölfel, E. M., Buravkova, L. B., Atiakshin, D., Markina, E. A., Schinke, T., Rolvien, T., Busse, B., & Jähn, K. (2021) · European Cells and Materials · doi:10.22203/ecm.v042a16 · Cited by 17 · see citing works
“during lactation (Jähn et al. 2017) or vitamin D deficiency (Rolvien et al.”
BackgroundSelf-citationRabelo, G. D., Scheidt, A. V., Klebig, F., Hemmatian, H., Çıtak, M., Amling, M., Busse, B., & Jähn, K. (2020) · Scientific Reports · doi:10.1038/s41598-019-57303-z · Cited by 17 · see citing works
Self-citationMurshid, S. A. (2022) · Tissue and Cell · doi:10.1016/j.tice.2022.101730 · Cited by 17 · see citing works
No Signature of Osteocytic Osteolysis in Cortical Bone from Lactating NMRI Mice
Wittig, N. K., Birkbak, M. E., Bach-Gansmo, F. L., Pacureanu, A., Wendelboe, M. H., Brüel, A., Thomsen, J. S., & Birkedal, H. (2019) · Calcified Tissue International · doi:10.1007/s00223-019-00569-2 · Cited by 16 · see citing works
Yajima, A., Tsuchiya, K., Burr, D. B., Minner, D. E., Condon, K. W., Miller, C. A., Satoh, S., Inaba, M., Nakayama, T., Tanizawa, T., et al. (2018) · Bone · doi:10.1016/j.bone.2018.05.002 · Cited by 15 · see citing works
Dedic, C., Hung, T. S., Shipley, A. M., Maeda, A., Gardella, T., Miller, A. L., Divieti Pajevic, P., Kunkel, J. G., & Rubinacci, A. (2018) · Bone · doi:10.1016/j.bone.2018.07.020 · Cited by 14 · see citing works
“Ca 2+ homeostasis through the reversible enlargement of the osteocyte lacunae and demineralization of the surrounding matrix under high Ca 2+ demand (38, 39, 65), our study raises the hypothesis that minute-to-minute maintenance of Ca 2+ equilibrium at the bone surfaces does not require any rapid action of PTH on the…”
InfluentialIntravital imaging of osteocyte integrin dynamics with locally injectable fluorescent nanoparticles
Matthews, M. D., Cook, E., Naguib, N., Wiesner, U. B., & Lewis, K. J. (2023) · Bone · doi:10.1016/j.bone.2023.116830 · Cited by 10 · see citing works
Deletion of FNDC5/irisin modifies murine osteocyte function in a sex-specific manner
Shimonty, A., Pin, F., Prideaux, M., Peng, G., Huot, J. R., Kim, H., Rosen, C. J., Spiegelman, B. M., & Bonewald, L. F. (2024) · eLife · doi:10.7554/elife.92263.3 · Cited by 13 · see citing works
Self-citationMoreno-Jiménez, I., Heinig, S., Heras, U., Maichl, D. S., Strifler, S., Leich, E., Blouin, S., Fratzl, P., Fratzl‐Zelman, N., Jundt, F., et al. (2024) · Bone · doi:10.1016/j.bone.2024.117236 · Cited by 13 · see citing works
Hongo, H., Hasegawa, T., Saito, M., Tsuboi, K., Yamamoto, T., Sasaki, M., Abe, M., Henrique Luiz de Freitas, P., Yurimoto, H., Udagawa, N., et al. (2020) · Journal of Histochemistry & Cytochemistry · doi:10.1369/0022155420961375 · Cited by 12 · see citing works
“For histological examination, other wild-type mice were anesthetized as described above and were then injected with 80 μg/kg/dose of hPTH [1-34] directly into the external jugular vein, whereas control mice were injected with the same volume of PBS.”
BackgroundMethodInfluentialDeletion of FNDC5/irisin modifies murine osteocyte function in a sex-specific manner
Shimonty, A., Pin, F., Prideaux, M., Peng, G., Huot, J. R., Kim, H., Rosen, C. J., Spiegelman, B. M., & Bonewald, L. F. (2023) · eLife · doi:10.7554/elife.92263 · Cited by 23 · see citing works
“In addition, there is an increase in genes coding for the proton pumps, ATPase H + trans-porting V1 subunit G1 ( Atp6v1g1 ), and ATPase H + transporting V0 subunit D2 ( Atp6v0d2 ) necessary to dissolve and remove calcium from bone collagen ( Jähn et al., 2017 ).”
BackgroundMethodInfluentialSelf-citationThe bone nonunion microenvironment: A place where osteogenesis struggles with osteoclastic capacity
Cheng, K., Gao, S., Mei, Y., Zhou, D., Song, C., Guo, D., Hou, Y., & Liu, Z. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e31314 · Cited by 12 · see citing works
“It has been found that ATP6V0D2 may be associated with osteoclast maturation, because in ATP6V0D2-deficient mice, there is a reduction in mature giant osteoclasts without altered osteoblast differentiation [72].”
BackgroundHow Important Is Vitamin D for Calcium Homeostasis During Pregnancy and Lactation?
Carmeliet, G., & Bouillon, R. (2017) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.3344 · Cited by 11 · see citing works
“The osteocytic bone resorption requires the action of PTH/PTHrP receptor in osteocytes((17)) and involves the activation of proton pumps (vacuolar ATPase) and other genes that were originally identified in relation to osteoclastic bone resorption.((17,18)) Whether the”
BackgroundKlein‐Nulend, J., & Bonewald, L. F. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-814841-9.00006-3 · Cited by 11 · see citing works
Self-citationWölfel, E. M., Lademann, F., Hemmatian, H., Blouin, S., Messmer, P., Hofbauer, L. C., Busse, B., Rauner, M., Jähn, K., & Tsourdi, E. A. (2020) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.4736 · Cited by 10 · see citing works
“Osteocytic osteolysis includes acidic removal of mineral from the perilacunar matrix of osteocytes.((25)) Here, we observed a 2.”
BackgroundInfluentialSelf-citationStachnik, K., Warmer, M., Mohacsi, I., Hennicke, V., Fischer, P., Meyer, J. H., Spitzbart, T., Barthelmeß, M., Eich, J., Dávid, C., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-58318-7 · Cited by 9 · see citing works
Self-citationHua, R., Truong, V. A., Fajardo, R. J., Guda, T., Gu, S., & Jiang, J. X. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.114363 · Cited by 8 · see citing works
Tumor Cell Secretomes in Response to Anti- and Pro-Tumorigenic Agents
Liu, S., Sun, X., Li, K., Lin, C., Na, S., Li, B., & Yokota, H. (2021) · Onco · doi:10.3390/onco1020009 · Cited by 8 · see citing works
Aging decreases osteocyte lacunar-canalicular turnover in female C57BL/6 mice
Vahidi, G., Boone, C., Hoffman, F., & Heveran, C. M. (2023) · Bone · doi:10.1016/j.bone.2024.117163 · Cited by 6 · see citing works
Fluorescent mapping of osteocyte-driven bone formation at pre-osteocyte and mature osteocyte lacunae
Ford, S., Tiedemann, K., Shapiro, R., Komarova, S. V., Jähn, K., & Zimmermann, E. A. (2025) · Acta Biomaterialia · doi:10.1016/j.actbio.2025.09.040 · Cited by 7 · see citing works
Self-citationCellular Contributors to Bone Homeostasis
Rauner, M., Jähn, K., Hemmatian, H., Colditz, J., & Goettsch, C. (2020) · Contemporary cardiology · doi:10.1007/978-3-030-46725-8_16 · Cited by 6 · see citing works
Self-citationSang, W., & Ural, A. (2023) · Journal of Biomechanical Engineering · doi:10.1115/1.4056655 · Cited by 6 · see citing works
Histological Assessment of Endochondral Ossification and Bone Mineralization
Hasegawa, T., Hongo, H., Yamamoto, T., Muneyama, T., Miyamoto, Y., & Amizuka, N. (2023) · Endocrines · doi:10.3390/endocrines4010006 · Cited by 5 · see citing works
Spatial control of perilacunar canalicular remodeling during lactation
Sieverts, M., Yee, C. S., Nemani, M., Parkinson, D. Y., Alliston, T. N., & Acevedo, C. (2024) · Scientific Reports · doi:10.1038/s41598-024-63645-0 · Cited by 5 · see citing works
The Impact of Non-bone Metastatic Cancer on Musculoskeletal Health
Galiana-Melendez, F., & Huot, J. (2024) · Current Osteoporosis Reports · doi:10.1007/s11914-024-00872-4 · Cited by 2 · see citing works
“If aberrantly elevated, PTHrP prompts osteocyte production of RANKL, thus stimulating osteoclast-induced bone resorption and osteocytic osteolysis [106].”
Jagga, S., Hughes, A., Arash, N. M., Sorsby, M., Brooks, D. J., Pajevic, P. D., & Liu, E. S. (2024) · Endocrinology · doi:10.1210/endocr/bqae087 · Cited by 3 · see citing works
Yee, C. S., Meliadis, C., Kaya, S., Chang, W., & Alliston, T. N. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1342938 · Cited by 4 · see citing works
Bonewald, L. F. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-813073-5.00007-1 · Cited by 4 · see citing works
Self-citationHashimoto, R., Minoshima, M., Kikuta, J., Yari, S., Bull, S. D., Ishii, M., & Kikuchi, K. (2020) · Angewandte Chemie · doi:10.1002/ange.202006388 · Cited by 4 · see citing works
Nakanishi, T., Yamazaki, M., Tachikawa, K., Ueta, A., Kawai, M., Ozono, K., & Michigami, T. (2024) · Bone · doi:10.1016/j.bone.2024.117044 · Cited by 4 · see citing works
The calcitonin receptor regulates osteocyte lacunae acidity during lactation in mice
Davey, R. A., Clarke, M. V., Golub, S. B., Russell, P. K., & Zajac, J. D. (2021) · Journal of Endocrinology · doi:10.1530/joe-20-0599 · Cited by 4 · see citing works
Radiotherapy-induced bone deterioration is exacerbated in diabetic rats treated with streptozotocin
Jiang, M., Ding, Y., Xu, S., Hao, X., Yang, Y., Luo, E., Jing, D., Yan, Z., & Cai, J. (2021) · Brazilian Journal of Medical and Biological Research · doi:10.1590/1414-431x2021e11550 · Cited by 4 · see citing works
Effects of Spinal Cord Injury and Related Conditions
Yarrow, J. F., & Cardozo, C. P. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-801238-3.11219-x · Cited by 5 · see citing works
Pregnancy, Lactation, and Bone Health
Miedany, Y. M. E. (2022) · Springer eBooks · doi:10.1007/978-3-030-87950-1_28 · Cited by 3 · see citing works
Coulombe, J. C., Mullen, Z., Weins, A. M., Fisher, L. E., Lynch, M. E., Stodieck, L., & Ferguson, V. L. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.01.04.474962 · Cited by 4 · see citing works
“in lacunar volume, as seen in our study, may be emblematic of osteocyte osteolysis (reduced mineralization) as 454 seen in lactation((8,9,12)), or bone metabolic disorders such as rickets((48)) or osteopenia((16)).”
BackgroundThe Scientific Case for Animal Models: A Perspective From Musculoskeletal Researchers
Hadjiargyrou, M., Hildreth, B. E., Ko, F., Sankar, U., & Yang, T. (2026) · FASEB BioAdvances · doi:10.1096/fba.2025-00313 · Cited by 2 · see citing works
Hongo, H., Yokoyama, A., Sekiguchi, T., Yamamoto, T., Yoshino, H., Abe, M., Haraguchi‐Kitakamae, M., de Freitas, P. H. L., Hasegawa, T., & Li, M. (2022) · Journal of Oral Biosciences · doi:10.1016/j.job.2022.09.003 · Cited by 2 · see citing works
Pei, S., Wasi, M., Wang, S., Chu, T., Guerra, R. M., & Wang, L. (2023) · Elsevier eBooks · doi:10.1016/b978-0-323-96123-3.00010-5 · Cited by 2 · see citing works
Sex specific effects of irisin on the skeleton
Shimonty, A., & Bonewald, L. F. (2026) · Bone Research · doi:10.1038/s41413-026-00542-4 · Cited by 1 · see citing works
“95,97 These sets of data suggest that the sex difference of a divergent osteocyte transcriptome is most likely due to the need for calcium in milk for the successful survival of offspring.”
Self-citationSuriano, C., Zerlotin, R., Taurino, M., Dicarlo, M., Storlino, G., Pignataro, P., Terrevoli, O. D., Pellicani, L., Oranger, A., Mori, G., et al. (2026) · Journal of Translational Medicine · doi:10.1186/s12967-026-08486-3 · Cited by 1 · see citing works
“The expression of the TRAP enzyme in osteocytes has been attributed to the process of osteocytic osteolysis [30].”
Memory T-Cells Contribute to Calcium Release from Bones during Lactation in Mice
Wu, D., Cline-Smith, A., Chrisler, B., Lubeck, B., Perla, A., Banerjee, S., Fan, I. X., & Aurora, R. (2024) · Nutrients · doi:10.3390/nu16193289 · Cited by 1 · see citing works
“This is likely because trabecular resorption is predominantly osteoclastic while cortical resorption is osteocytic, which is primarily driven by PTHrP during lactation [8–12].”
BackgroundBone-seeking tumor cells alter bone material quality parameters on the nanoscale in mice
Krug, J., Plumeyer, C., Davydok, A., Kolibová, S. D., Fischer, N., Le-Phuoc, X.-T., Rauner, M., Sihota, P., Schweizer, M., Busse, B., et al. (2024) · Biomaterials Advances · doi:10.1016/j.bioadv.2024.214060 · Cited by 1 · see citing works
Self-citationOsteocyte Mechanobiology in Aging and Disease
Donahue, H. J., Friendman, M. J., & Genetos, D. C. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-817931-4.00001-7 · Cited by 1 · see citing works
Technical approaches for studying the communications between osteocytes and cancer cells
Lin, C.-Y., Xu, L., & You, L. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-821666-8.00067-0 · Cited by 1 · see citing works
Moreno-Jiménez, I., Heinig, S., Heras, U., Maichl, D. S., Strifler, S., Leich, E., Blouin, S., Fratzl, P., Fratzl‐Zelman, N., Jundt, F., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.07.12.548656 · Cited by 1 · see citing works
Deletion of FNDC5/Irisin modifies murine osteocyte function in a sex-specific mannerPreprint
Shimonty, A., Pin, F., Prideaux, M., Peng, G., Huot, J. R., Kim, H., Rosen, C. J., Spiegelman, B. M., & Bonewald, L. F. (2024) · eLife · doi:10.7554/elife.92263.2 · Cited by 1 · see citing works
Self-citationMannstadt, M., & Wein, M. N. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-814841-9.00052-x
Osteocytes: More Than Just Mechanosensory Cells
Prideaux, M., & Bonewald, L. F. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-801238-3.11203-6
Self-citation
- Authors
- Jähn, K., Kelkar, S., Zhao, H., Xie, Y., Tiede-Lewis, L. M., Dusevich, V., Dallas, S. L., & Bonewald, L. F.
- Affiliations
- University of Missouri–Kansas City (US)
- Corresponding author
- Bonewald, Lynda F
- Venue
- Journal of Bone and Mineral Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2017-05-04
- Volume
- 32
- Issue
- 8
- Pages
- 1761-1772
- ISSN
- 0884-0431 (ISSN-L)
- 1523-4681
- PMC
- PMC5550338
- OpenAlex
- W2611717022
- Cited by
- 116
- References
- 39
- Citations by year
- 2026: 10 · 2025: 3 · 2024: 14 · 2023: 16 · 2022: 9 · 2021: 20 · 2020: 21 · 2019: 13 · 2018: 5 · 2017: 5
- FWCI
- 4.92
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Journal of Bone and Mineral Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (1PO1AG039355)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Alkaline Phosphatase Research Studies
- Keywords
- osteocytes, parathyroid hormone-related protein, lactation, calcium mobilization, vacuolar ATPase, ATP6V0D2, osteocyte viability, low calcium diet, bone matrix
- MeSH terms
- Animals, Cell Line, Transformed, Cell Survival, Female, Hydrogen-Ion Concentration, Lactation, Osteocytes, Macrolides, Vacuolar Proton-Translocating ATPases, Parathyroid Hormone-Related Protein, Mice, Cellular Microenvironment
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
