The DOI matches its Crossref record; 73 of the 74 references it cites were found in a registry or an index.
FOXP1 controls mesenchymal stem cell commitment and senescence during skeletal aging
Open accessAbstract
A hallmark of aged mesenchymal stem/progenitor cells (MSCs) in bone marrow is the pivot of differentiation potency from osteoblast to adipocyte coupled with a decrease in self-renewal capacity. However, how these cellular events are orchestrated in the aging progress is not fully understood. In this study, we have used molecular and genetic approaches to investigate the role of forkhead box P1 (FOXP1) in transcriptional control of MSC senescence. In bone marrow MSCs, FOXP1 expression levels declined with age in an inverse manner with those of the senescence marker p16INK4A. Conditional depletion of Foxp1 in bone marrow MSCs led to premature aging characteristics, including increased bone marrow adiposity, decreased bone mass, and impaired MSC self-renewal capacity in mice. At the molecular level, FOXP1 regulated cell-fate choice of MSCs through interactions with the CEBPβ/δ complex and recombination signal binding protein for immunoglobulin κ J region (RBPjκ), key modulators of adipogenesis and osteogenesis, respectively. Loss of p16INK4A in Foxp1-deficient MSCs partially rescued the defects in replication capacity and bone mass accrual. Promoter occupancy analyses revealed that FOXP1 directly represses transcription of p16INK4A. These results indicate that FOXP1 attenuates MSC senescence by orchestrating their cell-fate switch while maintaining their replicative capacity in a dose- and age-dependent manner.
Overview
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
Verification
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?
In the citing paper
“Ageing and genotoxic stress induce cellular senescence of these stem cells 96,97 and osteoprogenitor cells, 98,99 with subsequent decline in the functions of these cells in both mice and humans.100”
From The costs and benefits of senotherapeutics for human health (2022) · cites this paper as [98]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a
Serrano, M., Lin, A. W., McCurrach, M. E., Beach, D., & Lowe, S. W. (1997) · Cell · doi:10.1016/s0092-8674(00)81902-9 · Cited by 5,218 · cited 2×
“Tight transcriptional control of the p16 INK4A locus is important in regulating senescence of a number of adult stem cell lineages during aging (13, 14, 51, 52).”
Osf2/Cbfa1: A Transcriptional Activator of Osteoblast Differentiation
Ducy, P., Zhang, R., Geoffroy, V., Ridall, A. L., & Karsenty, G. (1997) · Cell · doi:10.1016/s0092-8674(00)80257-3 · Cited by 4,246
Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders
Baker, D. J., Wijshake, T., Tchkonia, T., LeBrasseur, N. K., Childs, B. G., van de Sluis, B., Kirkland, J. L., & van Deursen, J. M. (2011) · Nature · doi:10.1038/nature10600 · Cited by 3,670 · cited 1×
“Alterations in the transcriptional control or activity of these pathways account for the aging-related features detected in mice deficient for Bmi-1 (21), Brac1 (22), Zmpste24 (23), Hmga2 (24), or BUBR1 (25).”
Nakashima, K., Zhou, X., Kunkel, G., Zhang, Z., Deng, J. M., Behringer, R. R., & de Crombrugghe, B. (2002) · Cell · doi:10.1016/s0092-8674(01)00622-5 · Cited by 3,608
Mesenchymal and haematopoietic stem cells form a unique bone marrow niche
Méndez‐Ferrer, S., Michurina, T. V., Ferraro, F., Mazloom, A. R., MacArthur, B. D., Lira, S. A., Scadden, D. T., Ma’ayan, A., Enikolopov, G., & Frenette, P. S. (2010) · Nature · doi:10.1038/nature09262 · Cited by 3,381
Transcriptional control of adipocyte formation
Farmer, S. R. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.07.001 · Cited by 1,836
Cellular senescence in cancer and aging.
Collado, M., Blasco, M. A., & Serrano, M. (2007) · Cell · doi:10.1016/j.cell.2007.07.003 · Cited by 1,708
Jacobs, J. J. L., Kieboom, K., Marino, S., DePinho, R. A., & van Lohuizen, M. (1999) · Nature · doi:10.1038/16476 · Cited by 1,580
Ink4a/Arf expression is a biomarker of aging
Krishnamurthy, J., Torrice, C., Ramsey, M. R., Kovalev, G. I., Al-Regaiey, K., Su, L., & Sharpless, N. E. (2004) · Journal of Clinical Investigation · doi:10.1172/jci22475 · Cited by 1,486
p53 mutant mice that display early ageing-associated phenotypes
Tyner, S. D., Venkatachalam, S., Choi, J., Jones, S., Ghebranious, N., Igelmann, H., Lu, X., Soron, G., Cooper, B., Brayton, C., et al. (2002) · Nature · doi:10.1038/415045a · Cited by 1,459 · cited 1×
“…arrest, is mainly controlled by the p16 INK4A /Rb and p19 ARF /p53 pathways (13, 14). p16 INK4A is required for the age-associated decline in function of a number of adult stem cells (15–18), including BM MSCs (19). p53 -Deficient mice display osteoporosis and other aging-related features (20).”
Cited by
Sorted by citations
Senescent cells: an emerging target for diseases of ageing
Childs, B. G., Gluscevic, M., Baker, D. J., Laberge, R.-M., Marquess, D., Dananberg, J., & van Deursen, J. M. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2017.116 · Cited by 1,284
Lin, H., Sohn, J., Shen, H., Langhans, M. T., & Tuan, R. S. (2018) · Biomaterials · doi:10.1016/j.biomaterials.2018.06.026 · Cited by 455
“The expression of FOXP1in bone marrow MSCs decreased with the aging progress, and the conditional depletion of FOXP1 significantly accelerated MSCs aging in vivo [86].”
Osteoporosis and periodontal diseases – An update on their association and mechanistic links
Yu, B., & Wang, C. (2022) · Periodontology 2000 · doi:10.1111/prd.12422 · Cited by 437
Autophagy controls mesenchymal stem cell properties and senescence during bone aging
Ma, Y., Qi, M., An, Y., Zhang, L., Yang, R., Doro, D. H., Liu, W., & Jin, Y. J. (2017) · Aging Cell · doi:10.1111/acel.12709 · Cited by 349
“, 2004), increased reactive oxygen species (ROS) (Stolzing & Scutt, 2006) and transcriptional control (Li et al., 2017).”
BackgroundOsteogenesis and aging: lessons from mesenchymal stem cells
Infante, A., & Rodríguez, C. I. (2018) · Stem Cell Research & Therapy · doi:10.1186/s13287-018-0995-x · Cited by 334
Senile Osteoporosis: The Involvement of Differentiation and Senescence of Bone Marrow Stromal Cells
Qadir, A. S., Liang, S., Wu, Z., Chen, Z., Hu, L., & Qian, A. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21010349 · Cited by 279
“Moreover, it has been reported that forkhead box protein P1 (FOXP1) level is also decreased with age in both human and murine BMSCs, which results in bone loss [63] (Table 1).”
Underlying features of epigenetic aging clocks in vivo and in vitro.
Liu, Z., Leung, D., Thrush, K., Zhao, W., Ratliff, S., Tanaka, T., Schmitz, L. L., Smith, J. A., Ferrucci, L., & Levine, M. E. (2020) · Aging Cell · doi:10.1111/acel.13229 · Cited by 227
Long noncoding RNA Bmncr regulates mesenchymal stem cell fate during skeletal aging
Li, C., Xiao, Y., Yang, M., Su, T., Sun, X. H., Guo, Q., Huang, Y., & Luo, X. (2018) · Journal of Clinical Investigation · doi:10.1172/jci99044 · Cited by 235
“Discussion Age-related lineage switching of BMSCs between osteogenic and adipogenic fates is critical in age-associated osteoporosis (5, 6).”
Yu, B., Huo, L., Liu, Y., Deng, P., Szymanski, J. M., Li, J., Luo, X., Hong, C., Lin, J. D., & Wang, C. (2018) · Cell stem cell · doi:10.1016/j.stem.2018.06.009 · Cited by 196
Lin, Z., He, H., Wang, M., & Liang, J. (2019) · Cell Proliferation · doi:10.1111/cpr.12688 · Cited by 187
Gnani, D., Crippa, S., della Volpe, L., Rossella, V., Conti, A., Lettera, E., Rivis, S., Ometti, M., Fraschini, G., Bernardo, M. E., et al. (2019) · Aging Cell · doi:10.1111/acel.12933 · Cited by 188
Gan, Y., He, J., Zhu, J., Xu, Z., Wang, Z., Yan, J., Hu, O., Bai, Z., Chen, L., Xie, Y., et al. (2021) · Bone Research · doi:10.1038/s41413-021-00163-z · Cited by 173
Zhang, H., Xu, R., Li, B., Xin, Z., Ling, Z., Zhu, W., Li, X., Zhang, P., Fu, Y., Chen, J., et al. (2021) · Cell Death and Differentiation · doi:10.1038/s41418-021-00858-0 · Cited by 154
Spatiotemporal transcriptomic changes of human ovarian aging and the regulatory role of FOXP1
Wu, M., Tang, W., Chen, Y., Xue, L., Dai, J. Y., Li, Y., Zhu, X., Wu, C., Xiong, J., Zhang, J., et al. (2024) · Nature Aging · doi:10.1038/s43587-024-00607-1 · Cited by 159
The costs and benefits of senotherapeutics for human health
Raffaele, M., & Vinciguerra, M. (2022) · The Lancet Healthy Longevity · doi:10.1016/s2666-7568(21)00300-7 · Cited by 140
Mi, B., Xiong, Y., Knoedler, S. A., Alfertshofer, M. G., Panayi, A. C., Wang, H., Lin, S., Li, G., & Liu, G. (2024) · Bone Research · doi:10.1038/s41413-024-00346-4 · Cited by 147
“1 cells, observed in conditions like COVID-19.”
BackgroundMolecular Mechanisms Contributing to Mesenchymal Stromal Cell Aging
Neri, S., & Borzì, R. M. (2020) · Biomolecules · doi:10.3390/biom10020340 · Cited by 126
“It also downregulated polycomb proteins and upregulated miRNAs targeting polycomb proteins expression levels [79,80].”
BackgroundAli, D., Tencerova, M., Figeac, F., Kassem, M., & Jafari, A. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.981487 · Cited by 122
“Mouse genetic studies had shown that conditional depletion of Foxp1 in BMSCs leads to premature aging, bone loss, and increased BMA via Foxp1 interactions with different members of C/EBP family proteins, such as C/EBP b/d, which are key modulators of adipogenesis (38).”
BackgroundThe Long Non-coding RNA-ORLNC1 Regulates Bone Mass by Directing Mesenchymal Stem Cell Fate
Yang, L., Li, Y., Gong, R., Gao, M., Feng, C., Liu, T., Sun, Y., Jin, M., Wang, D., Yuan, Y., et al. (2018) · Molecular Therapy · doi:10.1016/j.ymthe.2018.11.019 · Cited by 117
“In certain inductive microenvironments, BMSCs can differentiate into a variety of cell types, such as osteoblasts, adipocytes, chondrocytes, neurons, myocytes, myoblasts, etc.(8) Such a property makes BMSCs an attractive candidate for cell therapy and tissue engineering.”
BackgroundAdult mesenchymal stem cell ageing interplays with depressed mitochondrial Ndufs6
Zhang, Y., Guo, L., Han, S., Chen, L., Li, C., Zhang, Z., Hong, Y., Zhang, X., Zhou, X., Jiang, D., et al. (2020) · Cell Death and Disease · doi:10.1038/s41419-020-03289-w · Cited by 112
Corrado, A., Cici, D., Rotondo, C., Maruotti, N., & Cantatore, F. P. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21103679 · Cited by 101
“In a murine model of accelerated senescence, the increase in ROS and the reduced BMD observed with age were associated with an increased expression of FoxO target genes as a defense mechanism and with a concomitant decreased expression of β-catenin/T-cell factor (TCF)-related genes.”
BackgroundInfluentialLiu, W., Zhang, L., Xuan, K., Hu, C., Liu, S., Liao, L., Li, B., Jin, F., Shi, S., & Jin, Y. J. (2018) · Bone Research · doi:10.1038/s41413-018-0029-4 · Cited by 100
Osteocytes regulate senescence of bone and bone marrow
Ding, P., Gao, C., Gao, Y., Liu, D., Li, H., Xu, J., Chen, X., Huang, Y., Zhang, C., Zheng, M., et al. (2022) · eLife · doi:10.7554/elife.81480 · Cited by 102
“Senescent 387 osteoprogenitors have reduced self-renewal capacity and predominantly differentiate 388 into adipocytes as opposed to osteoblasts (Chen, et al. 2016; Li et al. 2017; Rosen et 389 al.”
H3K36 trimethylation mediated by SETD2 regulates the fate of bone marrow mesenchymal stem cells
Wang, L., Niu, N., Li, L., Shao, R., Ouyang, H., & Zou, W. (2018) · PLoS Biology · doi:10.1371/journal.pbio.2006522 · Cited by 92
Epigenetic regulations of cellular senescence in osteoporosis
Huo, S., Tang, X., Chen, W., Gan, D., Guo, H., Yao, Q., Liao, R., Huang, T., Wu, J., Yang, J., et al. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102235 · Cited by 94
Macrophages in epididymal adipose tissue secrete osteopontin to regulate bone homeostasis
Dai, B., Xu, J., Li, X., Huang, L., Hopkins, C., Wang, H., Yao, H., Mi, J., Zheng, L., Wang, J., et al. (2022) · Nature Communications · doi:10.1038/s41467-021-27683-w · Cited by 92
Wei, X., Li, S., He, J., Du, H., Liu, Y., Yu, W., Hu, H., Han, L., Wang, C., Li, H., et al. (2019) · Cell Communication and Signaling · doi:10.1186/s12964-019-0373-z · Cited by 85
Splicing factor YBX1 regulates bone marrow stromal cell fate during aging
Xiao, Y., Cai, G., Xu, F., Li, Y., Guo, W., Guo, Q., Huang, Y., Su, T., Li, C., Luo, X., et al. (2023) · The EMBO Journal · doi:10.15252/embj.2022111762 · Cited by 77
The implications of bone marrow adipose tissue on inflammaging
Aaron, N., Costa, S., Rosen, C. J., & Qiang, L. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.853765 · Cited by 74
Liu, P., Huang, S., Ling, S., Xu, S., Wang, F., Zhang, W., Zhou, R., He, L., Xia, X., Yao, Z., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-12988-8 · Cited by 75
Biology of Tendon Stem Cells and Tendon in Aging
Lui, P. P. Y., & Wong, C. M. (2020) · Frontiers in Genetics · doi:10.3389/fgene.2019.01338 · Cited by 77
“It controlled MSC fate and senescence during skeletal aging (Li et al., 2017).”
BackgroundMechanistic advances in osteoporosis and anti‐osteoporosis therapies
Wang, H., Luo, Y., Wang, H., Li, F., Yu, F., & Ye, L. (2023) · MedComm · doi:10.1002/mco2.244 · Cited by 78
Li, T., Su, X., Lu, P., Kang, X., Hu, M., Li, C., Wang, S., Lu, D., Shen, S., Huang, H., et al. (2023) · Advanced Science · doi:10.1002/advs.202206432 · Cited by 75
Aging and lineage allocation changes of bone marrow skeletal (stromal) stem cells
Nehlin, J. O., Jafari, A., Tencerová, M., & Kassem, M. S. (2019) · Bone · doi:10.1016/j.bone.2019.03.041 · Cited by 68
“FOXP1 influenced adipose cell-fate through interactions with the C/EBPβ/δ key modulators of adipogenesis and directly repressed transcription of p16INK4A (47) (47).”
BackgroundHao, X., Shen, Y., Chen, N., Zhang, W., Valverde, E., Wu, L., Chan, H. L., Xu, Z., Yu, L., Gao, Y., et al. (2023) · Cell stem cell · doi:10.1016/j.stem.2023.04.005 · Cited by 74
Members of FOX family could be drug targets of cancers
Wang, J., Li, W., Zhao, Y., Kang, D., Fu, W., Zheng, X., Pang, X., & Du, G. (2017) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2017.08.003 · Cited by 66
The Differentiation Balance of Bone Marrow Mesenchymal Stem Cells Is Crucial to Hematopoiesis
Wu, J., Zhang, W., Ran, Q., Xiang, Y., Zhong, J. F., Li, S. C., & Li, Z. (2018) · Stem Cells International · doi:10.1155/2018/1540148 · Cited by 66
“Cellular senescence results in the decline of FOXP1 [84] and an increase in miR-188 [88], which correlate with reduced osteogenic differentiation and increased adipogenic differentiation.”
Stem Cell-Laden Hydrogel-Based 3D Bioprinting for Bone and Cartilage Tissue Engineering
Yang, Z., Yi, P., Liu, Z., Zhang, W., Mei, L., Feng, C., Tu, C., & Li, Z. (2022) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2022.865770 · Cited by 67
From Stem Cells to Bone-Forming Cells
Donsante, S., Palmisano, B., Serafini, M., Robey, P. G., Corsi, A., & Riminucci, M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22083989 · Cited by 66
“, oxidative stress [146], have been demonstrated to occur in BMSCs/SSCs both in vivo and in vitro [88,145], with consequent negative impact on their differentiation capacity and on their ability to regenerate bone.”
BackgroundInfluentialShen, W. X., Sun, B., Zhou, C., Ming, W., Zhang, S., & Wu, X. (2020) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.15792 · Cited by 62
The Mechanotransduction Signaling Pathways in the Regulation of Osteogenesis
Liu, Z., Wang, Q., Zhang, J., Qi, S., Duan, Y., & Li, C. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241814326 · Cited by 77
“TF Forkhead box P1 (FOXP1) stimulates both the osteogenic di ff erentiation of MSCs and the osteoblast mineralization [53,54].”
The Role of Adipose Stem Cells in Bone Regeneration and Bone Tissue Engineering
Mende, W., Götzl, R., Kubo, Y., Pufe, T., Ruhl, T., & Beier, J. P. (2021) · Cells · doi:10.3390/cells10050975 · Cited by 61
“Studies have shown that several osteogenic transcription factors are reduced in older MSCs, including MAF bZIP transcription factor [28], Forkhead box P1 [29], and Core-binding factor β [30].”
BackgroundBone Marrow Adipocytes: A Critical Player in the Bone Marrow Microenvironment
Wang, L., Zhang, H., Wang, S., Chen, X., & Su, J. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.770705 · Cited by 55
“Forkhead box P1 (FOXP1) can interact with the CEBPβ/δ complex and RBPjκ to regulate BMSC fate switches (Li et al., 2017).”
BackgroundCai, G., Liu, Y., Luo, L., Xiao, Y., Jiang, T.-J., Yuan, J., & Wang, M. (2022) · Cell Proliferation · doi:10.1111/cpr.13178 · Cited by 55
Fibroblasts as Turned Agents in Cancer Progression
Wieder, R. (2023) · Cancers · doi:10.3390/cancers15072014 · Cited by 55
Suo, J., Zou, S., Wang, J., Han, Y., Zhang, L., Lv, C., Jiang, B., Ren, Q., Chen, L., Yang, L., et al. (2022) · Bone Research · doi:10.1038/s41413-022-00202-3 · Cited by 52
“Existing studies on osteoporosis have mainly focused on transcription factors, epigenetics and hormone metabolism.(4,36,37) However, the mechanism of RNA-binding proteins involved in regulating osteoporosis remains to be discovered.”
BackgroundTargeting Cell Senescence for the Treatment of Age-Related Bone Loss
Pignolo, R. J., Samsonraj, R. M., Law, S. F., Wang, H., & Chandra, A. (2019) · Current Osteoporosis Reports · doi:10.1007/s11914-019-00504-2 · Cited by 52
Aging, obese-insulin resistance, and bone remodeling
Imerb, N., Thonusin, C., Chattipakorn, N., & Chattipakorn, S. C. (2020) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2020.111335 · Cited by 54
Inflammatory Microenvironment Accelerates Bone Marrow Mesenchymal Stem Cell Aging
Peng, X., Zhou, X. H., Yin, Y., Luo, B., Liu, Y., & Yang, C. (2022) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2022.870324 · Cited by 50
“It is well known that the lineage of the bone marrow cells changes with age and is characterized by an obvious reduction in osteogenesis and an increase in adipogenesis (Li et al., 2017; Infante and Rodríguez, 2018).”
BackgroundFOXP1 drives osteosarcoma development by repressing P21 and RB transcription downstream of P53
Li, H., Han, X., Yang, S., Wang, Y., Dong, Y., & Tang, T. (2021) · Oncogene · doi:10.1038/s41388-021-01742-4 · Cited by 48
Zhang, L., Guan, Q., Wang, Z., Feng, J., Zou, J., & Gao, B. (2023) · Aging and Disease · doi:10.14336/ad.2023.1115 · Cited by 58
“The expression of forkhead box protein 1 (FOXP1) [21], discoid domain receptor 2 (DDR2) [22], osteoprotegerin (OPG) [18, 19], osteoblast-specific transcription factor Runt-related transcription factor 2 (Runx2), distal-less homeobox 5 (Dlx5), the osteoblast marker collagen [20], peroxisome…”
Cellular senescence and hematological malignancies: From pathogenesis to therapeutics
Hu, D., Yuan, S., Zhong, J., Liu, Z., Wang, Y., Liu, L., Li, J., Wen, F., Liu, J., & Zhang, J. (2021) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2021.107817 · Cited by 47
BRD9-mediated chromatin remodeling suppresses osteoclastogenesis through negative feedback mechanism
Du, J., Liu, Y., Wu, X., Sun, J., Shi, J., Zhang, H., Ao, Z., Zhou, M., & Jiang, X. (2023) · Nature Communications · doi:10.1038/s41467-023-37116-5 · Cited by 48
Foxp2 regulates anatomical features that may be relevant for vocal behaviors and bipedal locomotion
Xu, S., Liu, P., Chen, Y., Chen, Y., Zhang, W., Zhao, H., Cao, Y., Wang, F., Jiang, N., Lin, S., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1721820115 · Cited by 42
“Our previous study demonstrated that Foxp1 promotes MSC osteogenic differentiation by repressing Notch signaling (36).”
Liu, W., Zhang, L., Xuan, K., Hu, C., Li, L., Zhang, Y., Jin, F., & Jin, Y. J. (2018) · Theranostics · doi:10.7150/thno.27372 · Cited by 44
“Currently, the regulators of lineage reciprocity of BMMSCs have all been identified as transcription factors [7-9], and researchers have not determined whether other genes control the lineage differentiation of BMMSCs.”
BackgroundXu, L., Wang, Y., Wang, J., Zhai, J., Ren, L., & Zhu, G. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22179323 · Cited by 43
Cellular senescence in tissue repair: every cloud has a silver lining
Yun, M. H. (2018) · The International Journal of Developmental Biology · doi:10.1387/ijdb.180081my · Cited by 44
“In the latter, it has recently been shown that the levels of the transcription factor FoxP1 decline during Ageing, leading to increases in p16 expression and MSC senescence.”
BackgroundCheng, K., Chen, I.-C., Cheng, C.-H. E., Mutoji, K. N., Hale, B. J., Hermann, B. P., Geyer, C. B., Oatley, J. M., & McCarrey, J. R. (2020) · iScience · doi:10.1016/j.isci.2020.101596 · Cited by 46
GATA6 regulates aging of human mesenchymal stem/stromal cells
Jiao, H., Walczak, B. E., Lee, M., Lemieux, M. E., & Li, W. (2020) · Stem Cells · doi:10.1002/stem.3297 · Cited by 38
“It has been reported that forkhead box P1 (FOXP1), another TF of the FOX family, plays a critical role in controlling fate commitment and senescence of mesenchymal stem cells (MSCs) during skeletal aging.(14) Nuclear factor-kappa B and paired box gene 5 have also been shown involved in the regulation of keratinocyte s…”
BackgroundAn, F., Wang, X., Wang, C., Liu, Y., Sun, B., Zhang, J., Gao, P., & Yan, C. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1210627 · Cited by 41
“However, during aging, or other pathological stimuli, BMSCs preferentially differentiate into adipocytes, resulting in an increase in bone marrow adipocytes and a decrease in osteoblasts and bone formation (14, 15).”
BackgroundYuan, K., Yang, Y., Lin, Y., Zhou, F., Huang, K., Yang, S., Kong, W., Li, F., Kan, T., Wang, Y., et al. (2024) · Advanced Science · doi:10.1002/advs.202404453 · Cited by 38
Ye, C., Chen, M., Chen, E., Li, W., Wang, S., Ding, Q., Wang, C., Zhou, C., Tang, L. F., Hou, W., et al. (2018) · Cell Death and Disease · doi:10.1038/s41419-018-0857-6 · Cited by 38
Mei, J., Zhou, F. L., Qiao, H., Li, H., & Tang, T. (2019) · Theranostics · doi:10.7150/thno.33908 · Cited by 38
“We performed western blotting as previously described [33], and the relative intensities of bands”
MethodBone metabolism regulation: Implications for the treatment of bone diseases
Yao, D., Huang, L., Ke, J., Zhang, M., Xiao, Q., & Zhu, X. M. (2020) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2020.110494 · Cited by 41
Neyroud, D., Nosacka, R. L., Callaway, C. S., Trevino, J. G., Hu, H., Judge, S. M., & Judge, A. R. (2021) · Journal of Cachexia Sarcopenia and Muscle · doi:10.1002/jcsm.12666 · Cited by 35
CGRP Regulates the Age-Related Switch Between Osteoblast and Adipocyte Differentiation
Li, H., Qu, J., Zhu, H., Wang, J., He, H., Xie, X., Wu, R., & Lu, Q. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.675503 · Cited by 37
Luo, Z., Wei, W., Qiu, D., Su, Z., Liu, L., Zhou, H., Cui, H., & Yang, L. (2024) · Bone Research · doi:10.1038/s41413-024-00351-7 · Cited by 37
“13 For example, modi fi cation of transcription factors, 6,7 epigenetics 10 – 14 and autophagy 5,15,16 that enhanced osteogenesis and decreased adipogenesis of BMSCs alleviated SOP in mice.”
BackgroundBai, M., Han, Y., Wu, Y., Liao, J., Li, L., Wang, L., Li, Q., Xing, W., Chen, L., Zou, W., et al. (2019) · PLoS Biology · doi:10.1371/journal.pbio.3000350 · Cited by 32
Liao, Z., Yu, J. H., Chu, Y., Wu, H., Li, X., Deng, Z., Feng, S., Chen, N., Luo, Z., Zheng, X., et al. (2022) · Communications Biology · doi:10.1038/s42003-022-03271-6 · Cited by 32
Rejuvenation of Mesenchymal Stem Cells to Ameliorate Skeletal Aging
Cheng, M., Yuan, W., Moshaverinia, A., & Yu, B. (2023) · Cells · doi:10.3390/cells12070998 · Cited by 33
“The main characteristics of senescent BM-MSCs include halted proliferation, reduced self-renewal and impaired differentiation, leading to “stem cell exhaustion” in vivo [28] and contributing to the impaired bone mass and delayed repair in long-bone [29,30].”
BackgroundLoss of Notch signaling in skeletal stem cells enhances bone formation with aging
Remark, L. H., Leclerc, K., Ramsukh, M., Lin, Z., Lee, S., Dharmalingam, B., Gillinov, L. A., Nayak, V. V., Parente, P. E., Sambon, M., et al. (2023) · Bone Research · doi:10.1038/s41413-023-00283-8 · Cited by 31
Mesenchymal stem cells and dental implant osseointegration during aging: from mechanisms to therapy
Ma, Y., Wang, S., Wang, H., Chen, X., Shuai, Y., Wang, H., Mao, Y., & He, F. (2023) · Stem Cell Research & Therapy · doi:10.1186/s13287-023-03611-1 · Cited by 35
“…have shown that the expression of transcription factors, including FOXP1, MAF, CBFβ, and SATB2, could potentially affect and attenuate senescence-related changes, including reduced bone mineral density, decreased trabecular thickness, and increased bone marrow adipogenic differentiation [55–58].”
BackgroundSenescent mesenchymal stem/stromal cells and restoring their cellular functions
Meng, Q., Liu, J., Lü, W., Fan, H., Zhou, X., & Liang, X. (2020) · World Journal of Stem Cells · doi:10.4252/wjsc.v12.i9.966 · Cited by 32
Chen, P., Hu, B., Xie, L., Jiang, T., Xia, Z., & Peng, H. (2021) · Cell Proliferation · doi:10.1111/cpr.13095 · Cited by 32
Li, H., Liang, J., Feng, Q. F., & Zhai, Y. (2018) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2018.09.161 · Cited by 30
Mesenchymal stem cells: ideal seeds for treating diseases
Gao, G., Fan, C., Li, J. W., Liang, R., Wei, C., Chen, X., Yang, Y., Zhong, Y., Shao, Y., Kong, Y., et al. (2021) · Human Cell · doi:10.1007/s13577-021-00578-0 · Cited by 29
FGFR2 accommodates osteogenic cell fate determination in human mesenchymal stem cells
Zhang, Y., Ling, L., Ajayakumar, A. A. D. O., Eio, M. Y., van Wijnen, A. J., Nurcombe, V., & Cool, S. M. (2022) · Gene · doi:10.1016/j.gene.2022.146199 · Cited by 30
Qiao, H., Mei, J., Yuan, K., Zhang, K., Zhou, F., Tang, T., & Zhao, J. (2022) · Journal of Nanobiotechnology · doi:10.1186/s12951-022-01536-0 · Cited by 30
“The supernatant was centrifuged at 4 °C for 20 min at 12,000 rpm, and a small amount of the supernatant was taken for western blot analysis as previously reported [74, 75].”
MethodLoss of KDM4B impairs osteogenic differentiation of OMSCs and promotes oral bone aging
Deng, P., Chang, I., Wang, J., Badreldin, A. A., Li, X., Yu, B., & Wang, C. (2022) · International Journal of Oral Science · doi:10.1038/s41368-022-00175-3 · Cited by 32
Massaro, F., Corrillon, F., Stamatopoulos, B., Meuleman, N., Lagneaux, L., & Bron, D. (2020) · Cancers · doi:10.3390/cancers13010068 · Cited by 28
“In mice, it has been shown that FOXP1, a transcription factor interacting with CEBPβ, is downregulated during aging [87].”
BackgroundAged mesenchymal stem cells and inflammation: from pathology to potential therapeutic strategies
Yang, X. F., Wang, Y., Rovella, V., Candi, E., Jia, W. P., Bernassola, F., Bove, P., Piacentini, M., Scimeca, M., Sica, G. S., et al. (2023) · Biology Direct · doi:10.1186/s13062-023-00394-6 · Cited by 28
Li, B., Wang, J., Xu, F., Wang, Q., Liu, Q., Wang, G., Miao, D., & Sun, Q. (2022) · Stem Cell Reviews and Reports · doi:10.1007/s12015-022-10408-x · Cited by 26
Li, Y., Hu, M., Xie, J., Li, S., & Dai, L. (2023) · Stem Cell Research & Therapy · doi:10.1186/s13287-023-03393-6 · Cited by 27
“Skeletal ageing is a progressive process that involves the inevitable exhaustion and senescence of BM-MSCs and a subsequent decline in bone homeostasis, accompanied by an elevated propensity for increased bone marrow adipose tissue (BMAT) and decreased bone mass [2, 12].”
BackgroundBone marrow adipocytes: key players in vascular niches, aging, and disease
Fan, Y., El-Khalek, M. K. A., Zhang, Y., Liu, L., Tian, Q., Chueakula, N., Ramasamy, S. K., Dalan, R., Habib, S. J., & Kusumbe, A. P. (2025) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2025.1633801 · Cited by 27
“The transcription factor FOXP1, which normally interacts with C/EBPβ/δ and Notch signaling to promote osteogenesis and restrain adipogenesis, is reduced with aging (Li et al., 2017).”
InfluentialТодосенко, Н. М., Хазиахматова, О. Г., Malashchenko, V. V., Yurova, K. A., Bograya, M., Beletskaya, M., Vulf, M. A., Mikhailova, L. V., Minchenko, A., Soroko, I., et al. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241512259 · Cited by 28
“In mouse models, FOXP1—a regulator of the pro-adipogenic CEBPβ/δ complex in BMAs–has been shown to attenuate aging by downregulating p16 INK4A (encoded by CDKN2A), a cell-cycle repressor that induces G1 phase arrest [76].”
BackgroundAwakening of Dormant Breast Cancer Cells in the Bone Marrow
Wieder, R. (2023) · Cancers · doi:10.3390/cancers15113021 · Cited by 26
The role of GATA4 in mesenchymal stem cell senescence: A new frontier in regenerative medicine
Babu, M. A., Renuka Jyothi, S., Kaur, I., Kumar, S., Sharma, N., Kumar, M., Rajput, P., Ali, H., Gupta, G., Subramaniyan, V., et al. (2024) · Regenerative Therapy · doi:10.1016/j.reth.2024.11.017 · Cited by 25
“Finally, overexpression of the FOXp1 effectuating vector was capable of immortalizing mesenchymal stem cells [87].”
Silencing circSERPINE2 restrains mesenchymal stem cell senescence via the YBX3/PCNA/p21 axis
Chen, F., Wang, S., Zeng, C., Tang, S., Gu, H., Wang, Z., Li, J., Feng, P., Zhang, Y., Wang, P., et al. (2023) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-023-04975-6 · Cited by 23
“Cellular senescence”
Li, J., Lu, L., Liu, Y., & Yu, X. (2021) · Journal of Molecular Medicine · doi:10.1007/s00109-021-02164-1 · Cited by 23
“Accordingly, declined FOXP1 in BMSCs from aged mice results in enlarged bone marrow adiposity and reduced bone mass [24].”
Liu, P., An, Y., Zhu, T., Tang, S., Huang, X., Li, S., Fu, F., Ji, C., & Xuan, K. (2023) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2023.1131218 · Cited by 25
“It has been well documented that BMMSCs suffer from reduced proliferation with a differentiation shift from osteogenesis to adipogenesis in osteopenias of diverse pathologies (Liu et al., 2016; Sui et al., 2016a; Li et al., 2017).”
BackgroundRegulation of osteogenesis via miR-101-3p in mesenchymal stem cells by human gingival fibroblasts
Kaneda‐Ikeda, E., Iwata, T., Mizuno, N., Nagahara, T., Kajiya, M., Ouhara, K., Yoshioka, M., Ishida, S., Kawaguchi, H., & Kurihara, H. (2020) · Journal of Bone and Mineral Metabolism · doi:10.1007/s00774-019-01080-2 · Cited by 23
“Moreover, FOXP1 controls MSC neural differentiation, commitment, and senescence [31, 32].”
BackgroundXu, Y., Chang, L., Chen, Y., Zhou, D., Zhou, L., Tang, J., Deng, L., Tang, G., & Li, C. (2024) · Advanced Science · doi:10.1002/advs.202406428 · Cited by 22
The Role of Forkhead Box Family in Bone Metabolism and Diseases
Xu, J., Wang, K., Zhang, Z., Xue, D., Li, W., & Pan, Z. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.772237 · Cited by 21
“found that FoxP1 favors bone formation over adipogenesis and may be a potential target gene for the treatment of osteoporosis (Li et al., 2017).”
BackgroundApplying causal discovery to single-cell analyses using CausalCell
Wen, Y., Huang, J., Zhang, H., Guo, S., Elyahu, Y., Monsonego, A., Ding, Y., & Zhu, H. (2023) · eLife · doi:10.7554/elife.81464 · Cited by 24
Downregulation of FOXP1 correlates with tendon stem/progenitor cells aging
Xu, H., & Liu, F. (2018) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2018.08.136 · Cited by 22
Tian, R.-C., Zhang, R., & Ma, C. (2025) · Biomolecules · doi:10.3390/biom15020276 · Cited by 23
“Conversely, the adipogenic potential of elderly BM-MSCs is increased [24].”
Li, J., Xie, R., Jiang, F., Li, Y., Zhu, Y. P., Liu, Z., Liao, M., Liu, Y., Meng, X., Chen, S., et al. (2021) · The FASEB Journal · doi:10.1096/fj.202100807rr · Cited by 21
Wang, T., Yang, L., Liang, Z., Bai, L., Pei, H., Zhang, T., Wu, L., Wang, L., Wang, X., You, X., et al. (2021) · Biomaterials Advances · doi:10.1016/j.msec.2021.112635 · Cited by 20
Wang, J., Xin, Y., Dong, Z., Li, S., & Yang, G. (2025) · Experimental Gerontology · doi:10.1016/j.exger.2025.112974 · Cited by 22
Differential regulation of skeletal stem/progenitor cells in distinct skeletal compartments
Solidum, J. G. N., Jeong, Y., Heralde, F. M., & Park, D. (2023) · Frontiers in Physiology · doi:10.3389/fphys.2023.1137063 · Cited by 20
“Forkhead box P1 (FOXP1) also declines with age, losing its anti-adipocyte interaction with C/EBPβ and proosteogenic repression of Notch signaling pathway, all leading to bone loss (Li et al., 2017).”
Background
Metadata
- Authors
- Li, H., Liu, P., Xu, S., Li, Y., Dekker, J. D., Li, B., Fan, Y., Zhang, Z., Hong, Y., Yang, G., Tang, T., Ren, Y., Tucker, H. O., Yao, Z., & Guo, X.
- Affiliations
- Shanghai Jiao Tong University (CN)
- Fudan University (CN)
- The University of Texas at Austin (US)
- Shanghai Sixth People's Hospital (CN)
- Nanjing First Hospital (CN)
- Corresponding author
- Guo, Xizhi
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 2017-02-27
- Volume
- 127
- Issue
- 4
- Pages
- 1241-1253
- ISSN
- 0021-9738 (ISSN-L)
- 1558-8238
- PMC
- PMC5373872
- OpenAlex
- W2591050028
- Cited by
- 180
- References
- 74
- Citations by year
- 2026: 8 · 2025: 22 · 2024: 24 · 2023: 33 · 2022: 27 · 2021: 18 · 2020: 18 · 2019: 9 · 2018: 18 · 2017: 3
- FWCI
- 7.54
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Lymphoma Research Foundation (300463)
- Cancer Prevention and Research Institute of Texas (RP120459, RP120348 and RP120459, RP120348)
- National Natural Science Foundation of China (973 Program, 31171396, 31100624, 2012CB966903, 31271553, 81421061, 81200586, 2014CB942902, R01CA31534)
- National Institutes of Health (31100624, 31271553, 2014CB942902, 31171396, 81421061, 2012CB966903)
- National Key Research and Development Program of China (31271553, 2012CB966903, R01CA31534, 31100624, 31171396, 2014CB942902, 81421061)
- National Cancer Institute (R01CA031534)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Keywords
- FOXP1, mesenchymal stem cells, skeletal aging, cellular senescence, p16INK4a, bone marrow adiposity, bone formation, adipogenesis, lineage commitment, transcriptional repression, replicative capacity, bone mass
- MeSH terms
- Animals, Bone Marrow Cells, Cell Line, Humans, Osteogenesis, Repressor Proteins, Cellular Senescence, Mice, Knockout, Cyclin-Dependent Kinase Inhibitor p16, CCAAT-Enhancer-Binding Protein-beta, Adipogenesis, Mice, CCAAT-Enhancer-Binding Protein-delta, Forkhead Transcription Factors, Mesenchymal Stem Cells
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
