Cited by 400

The DOI matches its Crossref record; 52 of the 52 references it cites were found in a registry or an index.

Sox9 Directs Hypertrophic Maturation and Blocks Osteoblast Differentiation of Growth Plate Chondrocytes

Open access

Dy, Peter, Wang, Weihuan, Bhattaram, Pallavi, Wang, Qiuqing, Wang, Lai, Ballock, R. Tracy, Lefebvre, Véronique·2012·Developmental Cell

DOI 10.1016/j.devcel.2011.12.024

Open this paper in CoChat — free account

Abstract

SUMMARY The transcription factor Sox9 is necessary for early chondrogenesis, but its subsequent roles in the cartilage growth plate, a highly specialized structure that drives skeletal growth and endochondral ossification, remain unclear. Using a doxycycline-inducible Cre transgene and Sox9 conditional null alleles in the mouse, we show that Sox9 is required to maintain chondrocyte columnar proliferation and generate cell hypertrophy, two key features of functional growth plates. Sox9 keeps Runx2 expression and β-catenin signaling in check, and thereby inhibits not only progression from proliferation to prehypertrophy, but also subsequent acquisition of an osteoblastic phenotype. Sox9 protein outlives Sox9 RNA in upper hypertrophic chondrocytes, where it contributes with Mef2c to directly activate the major marker of these cells, Col10a1. These findings thus reveal that Sox9 remains a central determinant of the lineage fate and multi-step differentiation program of growth plate chondrocytes, and thereby illuminate our understanding of key molecular mechanisms underlying skeletogenesis.

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

Crossref · 10.1016/j.devcel.2011.12.024

Cites

52 of 52 references verified0 citation errors · 0 not checkable

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.

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

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
Targeted Disruption of Results in a Complete Lack of Bone Formation owing to Maturational Arrest of Osteoblasts
Komori, T., Yagi, H., Nomura, S., Yamaguchi, A., Sasaki, K., Deguchi, K., Shimizu, Y., Bronson, R. T., Gao, Y.-H., Inada, M., et al. (1997) · Cell · doi:10.1016/s0092-8674(00)80258-5 · Cited by 4,244
The Novel Zinc Finger-Containing Transcription Factor Osterix Is Required for Osteoblast Differentiation and Bone Formation
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
Burden of major musculoskeletal conditions.
(2003) · Europe PMC (PubMed Central) · Cited by 3,521
A global double-fluorescent Cre reporter mouse
Muzumdar, M. D., Tasic, B., Miyamichi, K., Li, L., & Luo, L. (2007) · genesis · doi:10.1002/dvg.20335 · Cited by 3,491
Cbfa1, a Candidate Gene for Cleidocranial Dysplasia Syndrome, Is Essential for Osteoblast Differentiation and Bone Development
Otto, F., Thornell, A. P., Crompton, T., Denzel, A., Gilmour, K. C., Rosewell, I. R., Stamp, G. W. H., Beddington, R. S. P., Mundlos, S., Olsen, B. R., et al. (1997) · Cell · doi:10.1016/s0092-8674(00)80259-7 · Cited by 2,814
Sox9 is required for cartilage formation
Bi, W., Deng, J. M., Zhang, Z., Behringer, R. R., & de Crombrugghe, B. (1999) · Nature Genetics · doi:10.1038/8792 · Cited by 1,758
Indian hedgehog signaling regulates proliferation and differentiation of chondrocytes and is essential for bone formation
St-Jacques, B., Hammerschmidt, M., & McMahon, A. P. (1999) · Genes & Development · doi:10.1101/gad.13.16.2072 · Cited by 1,735
The transcription factor Sox9 has essential roles in successive steps of the chondrocyte differentiation pathway and is required for expression of Sox5 and Sox6
Akiyama, H., Chaboissier, M.-C., Martin, J. F., Schedl, A., & de Crombrugghe, B. (2002) · Genes & Development · doi:10.1101/gad.1017802 · Cited by 1,721
Autosomal sex reversal and campomelic dysplasia are caused by mutations in and around the SRY-related gene SOX9
Wagner, T., Wirth, J., Meyer, J., Zabel, B., Held, M., Zimmer, J., Pasantes, J., Bricarelli, F. D., Keutel, J., Hustert, E., et al. (1994) · Cell · doi:10.1016/0092-8674(94)90041-8 · Cited by 1,618
Wnt/β-Catenin Signaling in Mesenchymal Progenitors Controls Osteoblast and Chondrocyte Differentiation during Vertebrate Skeletogenesis
Day, T. F., Guo, X., Garrett-Beal, L., & Yang, Y. (2005) · Developmental Cell · doi:10.1016/j.devcel.2005.03.016 · Cited by 1,616
Campomelic dysplasia and autosomal sex reversal caused by mutations in an SRY-related gene
Foster, J. W., Dominguez-Steglich, M. A., Guioli, S., Kwok, C., Weller, P. A., Stevanović, M., Weissenbach, J., Mansour, S., Young, I. D., Goodfellow, P. N., et al. (1994) · Nature · doi:10.1038/372525a0 · Cited by 1,612
Intestinal polyposis in mice with a dominant stable mutation of the beta -catenin gene
Harada, N. (1999) · The EMBO Journal · doi:10.1093/emboj/18.21.5931 · Cited by 1,212
Canonical Wnt/β-Catenin Signaling Prevents Osteoblasts from Differentiating into Chondrocytes
Hill, T. P., Später, D., Taketo, M. M., Birchmeier, W., & Hartmann, C. (2005) · Developmental Cell · doi:10.1016/j.devcel.2005.02.013 · Cited by 1,084
Expression of Cre recombinase in the developing mouse limb bud driven by a Prxl enhancer
Logan, M., Martin, J. F., Nagy, A., Lobe, C., Olson, E. N., & Tabin, C. J. (2002) · genesis · doi:10.1002/gene.10092 · Cited by 1,005
Osteoblast Precursors, but Not Mature Osteoblasts, Move into Developing and Fractured Bones along with Invading Blood Vessels
Maes, C., Kobayashi, T., Selig, M. K., Torrekens, S., Roth, S. I., Mackem, S., Carmeliet, G., & Kronenberg, H. M. (2010) · Developmental Cell · doi:10.1016/j.devcel.2010.07.010 · Cited by 940
A new long form of Sox5 (L‐Sox5), Sox6 and Sox9 are coexpressed in chondrogenesis and cooperatively activate the type II collagen gene
Lefebvre, V., Li, P., & de Crombrugghe, B. (1998) · The EMBO Journal · doi:10.1093/emboj/17.19.5718 · Cited by 811
Self-citation
Histone Deacetylase 4 Controls Chondrocyte Hypertrophy during Skeletogenesis
Vega, R. B., Matsuda, K., Oh, J., Barbosa, A. C., Yang, X., Meadows, E., McAnally, J., Pomajzl, C., Shelton, J. M., Richardson, J. A., et al. (2004) · Cell · doi:10.1016/j.cell.2004.10.024 · Cited by 804
The circuitry of a master switch: Myod and the regulation of skeletal muscle gene transcription
Tapscott, S. J. (2005) · Development · doi:10.1242/dev.01874 · Cited by 763
Interactions between Sox9 and β-catenin control chondrocyte differentiation
Akiyama, H., Lyons, J. P., Mori-Akiyama, Y., Yang, X., Zhang, R., Zhang, Z., Deng, J. M., Taketo, M. M., Nakamura, T., Behringer, R. R., et al. (2004) · Genes & Development · doi:10.1101/gad.1171104 · Cited by 754
Genetic Control of Bone Formation
Karsenty, G., Kronenberg, H. M., & Settembre, C. (2009) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.042308.113308 · Cited by 667
Haploinsufficiency of Sox9 results in defective cartilage primordia and premature skeletal mineralization
Bi, W., Huang, W., Whitworth, D. J., Deng, J. M., Zhang, Z., Behringer, R. R., & de Crombrugghe, B. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.111092198 · Cited by 541
Continuous expression of Cbfa1 in nonhypertrophic chondrocytes uncovers its ability to induce hypertrophic chondrocyte differentiation and partially rescues Cbfa1-deficient mice
Takeda, S., Bonnamy, J.-P., Owen, M. J., Ducy, P., & Karsenty, G. (2001) · Genes & Development · doi:10.1101/gad.845101 · Cited by 518
Transcriptional control of chondrocyte fate and differentiation
Lefebvre, V., & Smits, P. (2005) · Birth Defects Research Part C: Embryo Today: Reviews · doi:10.1002/bdrc.20048 · Cited by 476
Self-citation
MEF2C Transcription Factor Controls Chondrocyte Hypertrophy and Bone Development
Arnold, M. A., Kim, Y., Czubryt, M. P., Phan, D., McAnally, J., Qi, X., Shelton, J. M., Richardson, J. A., Bassel-Duby, R., & Olson, E. N. (2007) · Developmental Cell · doi:10.1016/j.devcel.2007.02.004 · Cited by 456
Sox9 is required for determination of the chondrogenic cell lineage in the cranial neural crest
Mori-Akiyama, Y., Akiyama, H., Rowitch, D. H., & de Crombrugghe, B. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1631288100 · Cited by 429
Molecular mechanisms of endochondral bone development
Provot, S., & Schipani, E. (2005) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2004.11.068 · Cited by 375
The combination of SOX5, SOX6, and SOX9 (the SOX trio) provides signals sufficient for induction of permanent cartilage
Ikeda, T., Kamekura, S., Mabuchi, A., Kou, I., Seki, S., Takato, T., Nakamura, K., Kawaguchi, H., Ikegawa, S., & Chung, U. (2004) · Arthritis & Rheumatism · doi:10.1002/art.20611 · Cited by 357
Developmental Regulation of Wnt/β-Catenin Signals Is Required for Growth Plate Assembly, Cartilage Integrity, and Endochondral Ossification
Tamamura, Y., Otani, T., Kanatani, N., Koyama, E., Kitagaki, J., Komori, T., Yamada, Y., Costantini, F., Wakisaka, S., Pacifici, M., et al. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m414275200 · Cited by 334
Type X collagen gene regulation by Runx2 contributes directly to its hypertrophic chondrocyte–specific expression in vivo
Zheng, Q., Zhou, G., Morello, R., Chen, Y., Garcia-Rojas, X., & Lee, B. (2003) · The Journal of Cell Biology · doi:10.1083/jcb.200211089 · Cited by 331
L-Sox5 and Sox6 Drive Expression of the Aggrecan Gene in Cartilage by Securing Binding of Sox9 to a Far-Upstream Enhancer
Han, Y., & Lefebvre, V. (2008) · Molecular and Cellular Biology · doi:10.1128/mcb.00695-08 · Cited by 302
Self-citation
Control of chondrogenesis by the transcription factor Sox9
Akiyama, H. (2008) · Modern Rheumatology · doi:10.1007/s10165-008-0048-x · Cited by 285
SOX9 is a major negative regulator of cartilage vascularization, bone marrow formation and endochondral ossification
Hattori, T., Müller, C., Gebhard, S., Bauer, E., Pausch, F., Schlund, B., Bösl, M. R., Hess, A., Surmann-Schmitt, C., von der Mark, H., et al. (2010) · Development · doi:10.1242/dev.045203 · Cited by 275
Potent Inhibition of the Master Chondrogenic FactorSox9 Gene by Interleukin-1 and Tumor Necrosis Factor-α
Murakami, S., Lefebvre, V., & de Crombrugghe, B. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.5.3687 · Cited by 269
Self-citation
The chondrogenic transcription factor Sox9 is a target of signaling by the parathyroid hormone-related peptide in the growth plate of endochondral bones
Huang, W., Chung, U.-I., Kronenberg, H. M., & de Crombrugghe, B. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.98.1.160 · Cited by 243
Temporal, spatial, and cell type–specific control of Cre-mediated DNA recombination in transgenic mice
Utomo, A. R. H., Nikitin, A. Y., & Lee, W.-H. (1999) · Nature Biotechnology · doi:10.1038/15073 · Cited by 236
Sox9 Inhibits Wnt Signaling by Promoting β-Catenin Phosphorylation in the Nucleus
Topol, L., Chen, W., Song, H., Day, T. F., & Yang, Y. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m808048200 · Cited by 230
Wnt9a signaling is required for joint integrity and regulation of Ihh during chondrogenesis
Später, D., Hill, T. P., O'Sullivan, R. J., Gruber, M., Conner, D. A., & Hartmann, C. (2006) · Development · doi:10.1242/dev.02471 · Cited by 219
Organogenesis relies on SoxC transcription factors for the survival of neural and mesenchymal progenitors
Bhattaram, P., Penzo-Méndez, A., Sock, E., Colmenares, C., Kaneko, K. J., Vassilev, A., DePamphilis, M. L., Wegner, M., & Lefebvre, V. (2010) · Nature Communications · doi:10.1038/ncomms1008 · Cited by 217
Self-citation
Sox9 sustains chondrocyte survival and hypertrophy in part through Pik3ca-Akt pathways
Ikegami, D., Akiyama, H., Suzuki, A., Nakamura, T., Nakano, T., Yoshikawa, H., & Tsumaki, N. (2011) · Development · doi:10.1242/dev.057802 · Cited by 187
Sox5 and Sox6 are needed to develop and maintain source, columnar, and hypertrophic chondrocytes in the cartilage growth plate
Smits, P., Dy, P., Mitra, S., & Lefebvre, V. (2004) · The Journal of Cell Biology · doi:10.1083/jcb.200312045 · Cited by 172
Self-citation
The Transcriptional Activity of Sox9 in Chondrocytes Is Regulated by RhoA Signaling and Actin Polymerization
Kumar, D. V., & Lassar, A. B. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.01779-08 · Cited by 154
Loss of DNA-dependent dimerization of the transcription factor SOX9 as a cause for campomelic dysplasia
Sock, E. (2003) · Human Molecular Genetics · doi:10.1093/hmg/ddg158 · Cited by 142
Parathyroid Hormone-Related Peptide Represses Chondrocyte Hypertrophy through a Protein Phosphatase 2A/Histone Deacetylase 4/MEF2 Pathway
Kozhemyakina, E. A., Cohen, T., Yao, T., & Lassar, A. B. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.00415-09 · Cited by 141
Multiple roles of mesenchymal β-catenin during murine limb patterning
Hill, T. P., Taketo, M. M., Birchmeier, W., & Hartmann, C. (2006) · Development · doi:10.1242/dev.02298 · Cited by 129
Conditional inactivation of Sox9: A mouse model for campomelic dysplasia
Kist, R., Schrewe, H., Balling, R., & Scherer, G. (2002) · genesis · doi:10.1002/gene.10050 · Cited by 111
The Wnt/β-Catenin Pathway Interacts Differentially with PTHrP Signaling to Control Chondrocyte Hypertrophy and Final Maturation
Guo, X., Mak, K. K., Taketo, M. M., & Yang, Y. (2009) · PLoS ONE · doi:10.1371/journal.pone.0006067 · Cited by 87
Thyroid Hormone Interacts With the Wnt/β-Catenin Signaling Pathway in the Terminal Differentiation of Growth Plate Chondrocytes
Wang, L., Shao, Y. Y., & Ballock, R. T. (2007) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.070806 · Cited by 85
Self-citation
Runx2 contributes to murine Col10a1 gene regulation through direct interaction with its cis-enhancer
Li, F., Lu, Y., Ding, M., Napierala, D., Abbassi, S., Chen, Y., Duan, X., Wang, S., Lee, B., & Zheng, Q. (2011) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.504 · Cited by 78
Synovial joint morphogenesis requires the chondrogenic action of Sox5 and Sox6 in growth plate and articular cartilage
Dy, P., Smits, P. J., Silvester, A., Penzo‐Méndez, A., Dumitriu, B., Han, Y., de la Motte, C. A., Kingsley, D. M., & Lefebvre, V. (2010) · Developmental Biology · doi:10.1016/j.ydbio.2010.02.024 · Cited by 77
Self-citation
Role of Runx Proteins in Chondrogenesis
Yoshida, C. A., & Komori, T. (2005) · Critical Reviews in Eukaryotic Gene Expression · doi:10.1615/critreveukargeneexpr.v15.i3.60 · Cited by 64
Localization of the Cis-Enhancer Element for Mouse Type X Collagen Expression in Hypertrophic Chondrocytes In Vivo
Zheng, Q., Keller, B., Zhou, G. D., Napierala, D., Chen, Y., Zabel, B., Parker, A. E., & Lee, B. (2008) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.081249 · Cited by 30

Sox9 Modulates Proliferation and Expression of Osteogenic Markers of Adipose-Derived Stem Cells (ASC)
Stöckl, S., Göttl, C., Grifka, J., & Grässel, S. (2013) · Cellular Physiology and Biochemistry · doi:10.1159/000350089 · Cited by 4,656
Cellular biology of fracture healing
Bahney, C. S., Zondervan, R. L., Allison, P., Theologis, A., Ashley, J. W., Ahn, J., Miclau, T., Marcucio, R. S., & Hankenson, K. D. (2019) · Journal of Orthopaedic Research · doi:10.1002/jor.24170 · Cited by 577
Sox proteins: regulators of cell fate specification and differentiation
Kamachi, Y., & Kondoh, H. (2013) · Development · doi:10.1242/dev.091793 · Cited by 572
Palaeoproteomic evidence identifies archaic hominins associated with the Châtelperronian at the Grotte du Renne
Welker, F., Hajdinjak, M., Talamo, S., Jaouen, K., Dannemann, M., David, F., Julien, M., Meyer, M., Kelso, J., Barnes, I., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1605834113 · Cited by 309
The transcription factors SOX9 and SOX5/SOX6 cooperate genome-wide through super-enhancers to drive chondrogenesis
Liu, C.-F., & Lefebvre, V. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv688 · Cited by 287
Self-citation

See all 400

Authors: Dy, P., Wang, W., Bhattaram, P., Wang, Q., Wang, L., Ballock, R. T., & Lefebvre, V.
Venue: Developmental Cell
Publisher: Elsevier BV
Published: 2012-03
Volume: 22
Issue: 3
Pages: 597-609
ISSN: 1534-5807 (ISSN-L)
DOI: 10.1016/j.devcel.2011.12.024
OpenAlex: W2011576192
Cited by: 400
References: 52
FWCI: 20.25
Type: journal article
Language: en
Open access: bronze

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

Data sources

Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.

Sox9 Directs Hypertrophic Maturation and Blocks Osteoblast Differentiation of Growth Plate Chondrocytes

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Self-check

Citations

Cites

Cited by

Metadata

Record

About these checks

Data sources