The DOI matches its Crossref record; 67 of the 68 references it cites were found in a registry or an index.
Osteocyte necrosis triggers osteoclast-mediated bone loss through macrophage-inducible C-type lectin
Open accessAbstract
Although the control of bone-resorbing osteoclasts through osteocyte-derived RANKL is well defined, little is known about the regulation of osteoclasts by osteocyte death. Indeed, several skeletal diseases, such as bone fracture, osteonecrosis, and inflammation are characterized by excessive osteocyte death. Herein we show that osteoclasts sense damage-associated molecular patterns (DAMPs) released by necrotic osteocytes via macrophage-inducible C-type lectin (Mincle), which induced their differentiation and triggered bone loss. Osteoclasts showed robust Mincle expression upon exposure to necrotic osteocytes in vitro and in vivo. RNA sequencing and metabolic analyses demonstrated that Mincle activation triggers osteoclastogenesis via ITAM-based calcium signaling pathways, skewing osteoclast metabolism toward oxidative phosphorylation. Deletion of Mincle in vivo effectively blocked the activation of osteoclasts after induction of osteocyte death, improved fracture repair, and attenuated inflammation-mediated bone loss. Furthermore, in patients with osteonecrosis, Mincle was highly expressed at skeletal sites of osteocyte death and correlated with strong osteoclastic activity. Taken together, these data point to what we believe is a novel DAMP-mediated process that allows osteoclast activation and bone loss in the context of osteocyte death.
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“DAMPs can directly regulate osteoclast formation by activating the membrane-bound C-type lectin receptor Mincle. Mincle activation triggers calcium signaling and oxidative phosphorylation in osteoclasts, inducing osteoclast differentiation.74”
From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [74]
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Cites
Pattern Recognition Receptors and Inflammation
Takeuchi, O., & Akira, S. (2010) · Cell · doi:10.1016/j.cell.2010.01.022 · Cited by 8,895
Osteoclast differentiation and activation
Boyle, W. J., Simonet, W. S., & Lacey, D. L. (2003) · Nature · doi:10.1038/nature01658 · Cited by 6,670 · cited 2×
“This rather well-understood process is orchestrated by blood-derived monocytes that differentiate into bone-resorbing osteoclasts (1).”
BackgroundCirculating mitochondrial DAMPs cause inflammatory responses to injury
Zhang, Q., Raoof, M., Chen, Y., Sumi, Y., Sursal, T., Junger, W., Brohi, K., Itagaki, K., & Hauser, C. J. (2010) · Nature · doi:10.1038/nature08780 · Cited by 3,812
Bonewald, L. F. (2011) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.320 · Cited by 2,287
Fracture healing: mechanisms and interventions
Einhorn, T. A., & Gerstenfeld, L. C. (2014) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2014.164 · Cited by 1,902
Evidence for osteocyte regulation of bone homeostasis through RANKL expression
Nakashima, T., Hayashi, M., Fukunaga, T., Kurata, K., Oh-hora, M., Feng, J. Q., Bonewald, L. F., Kodama, T., Wutz, A., Wagner, E. F., et al. (2011) · Nature Medicine · doi:10.1038/nm.2452 · Cited by 1,778
Genetic regulation of osteoclast development and function
Teitelbaum, S. L., & Ross, F. P. (2003) · Nature Reviews Genetics · doi:10.1038/nrg1122 · Cited by 1,720
The ovariectomized rat model of postmenopausal bone loss
Kalu, D. N. (1991) · Bone and Mineral · doi:10.1016/0169-6009(91)90124-i · Cited by 1,364
Matrix-embedded cells control osteoclast formation
Xiong, J., Onal, M., Jilka, R. L., Weinstein, R. S., Manolagas, S. C., & O'Brien, C. A. (2011) · Nature Medicine · doi:10.1038/nm.2448 · Cited by 1,304
Damage-associated molecular patterns in inflammatory diseases
Roh, J. S., & Sohn, D. H. (2018) · Immune Network · doi:10.4110/in.2018.18.e27 · Cited by 1,261
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Mechanical regulation of bone remodeling
Wang, L., You, X., Zhang, L., Zhang, C., & Zou, W. (2022) · Bone Research · doi:10.1038/s41413-022-00190-4 · Cited by 641
Bone remodeling: an operational process ensuring survival and bone mechanical competence
Bolamperti, S., Villa, I., & Rubinacci, A. (2022) · Bone Research · doi:10.1038/s41413-022-00219-8 · Cited by 482
The role of autophagy in bone metabolism and clinical significance
Wang, J., Zhang, Y., Cao, J., Wang, Y., Anwar, N., Zhang, Z., Zhang, D., Ma, Y., Xiao, Y., Xiao, L., et al. (2023) · Autophagy · doi:10.1080/15548627.2023.2186112 · Cited by 337
Targeting ferroptosis suppresses osteocyte glucolipotoxicity and alleviates diabetic osteoporosis
Yang, Y., Lin, Y., Wang, M., Yuan, K., Wang, Q., Mu, P., Du, J., Yu, Z., Yang, S., Huang, K., et al. (2022) · Bone Research · doi:10.1038/s41413-022-00198-w · Cited by 267
Targeting strategies for bone diseases: signaling pathways and clinical studies
Xu, H., Wang, W., Liu, X., Huang, W. H., Chen, Z., Xu, Y., Yang, H., Bai, J., & Geng, D. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01467-8 · Cited by 177
Metadata
- Authors
- Andreev, D., Liu, M., Weidner, D., Kachler, K., Faas, M., Grüneboom, A., Schlötzer-Schrehardt, U., Muñoz, L. E., Steffen, U., Grötsch, B., Killy, B., Krönke, G., Luebke, A. M., Niemeier, A., Wehrhan, F., Lang, R., Schett, G., & Bozec, A.
- Affiliations
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- University Medical Center Hamburg-Eppendorf (DE)
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 2020-08-10
- Volume
- 130
- Issue
- 9
- Pages
- 4811-4830
- ISSN
- 0021-9738 (ISSN-L)
- 1558-8238
- PMC
- PMC7456234
- OpenAlex
- W3047914933
- Cited by
- 188
- References
- 68
- Citations by year
- 2026: 25 · 2025: 38 · 2024: 41 · 2023: 35 · 2022: 24 · 2021: 19 · 2020: 6
- FWCI
- 6.81
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (CRC‐1181, FOR 2886 (TP02, FOR2886, BO‐3811/5‐1, BO-3811/6-1)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Health Sciences › Medicine › Rheumatology › Osteomyelitis and Bone Disorders Research
- Keywords
- osteoclastogenesis, Mincle, damage-associated molecular patterns, bone loss, avascular necrosis, fracture healing, ITAM signaling, calcium signaling, oxidative phosphorylation, RANKL
- MeSH terms
- RNA-Seq, Animals, Bone Resorption, Membrane Proteins, Necrosis, Osteoclasts, Osteocytes, Mice, Knockout, Lectins, C-Type, Mice
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