Role of Runx genes in chondrocyte differentiation - PubMed (original) (raw)
. 2002 May 1;245(1):95-108.
doi: 10.1006/dbio.2002.0640.
Affiliations
- PMID: 11969258
- DOI: 10.1006/dbio.2002.0640
Free article
Role of Runx genes in chondrocyte differentiation
Sigmar Stricker et al. Dev Biol. 2002.
Free article
Abstract
Runx2/Cbfa1 plays a central role in skeletal development as demonstrated by the absence of osteoblasts/bone in mice with inactivated Runx2/Cbfa1 alleles. To further investigate the role of Runx2 in cartilage differentiation and to assess the potential of Runx2 to induce bone formation, we cloned chicken Runx2 and overexpressed it in chick embryos using a retroviral system. Infected chick wings showed multiple phenotypes consisting of (1) joint fusions, (2) expansion of carpal elements, and (3) shortening of skeletal elements. In contrast, bone formation was not affected. To investigate the function of Runx2/Cbfa1 during cartilage development, we have generated transgenic mice that express a dominant negative form of Runx2 in cartilage. The selective inactivation of Runx2 in chondrocytes results in a severe shortening of the limbs due to a disturbance in chondrocyte differentiation, vascular invasion, osteoclast differentiation, and periosteal bone formation. Analysis of the growth plates in transgenic mice and in chick limbs shows that Runx2 is a positive regulator of chondrocyte differentiation and vascular invasion. The results further indicate that Runx2 promotes chondrogenesis either by maintaining or by initiating early chondrocyte differentiation. Furthermore, Runx2 is essential but not sufficient to induce osteoblast differentiation. To analyze the role of runx genes in skeletal development, we performed in situ hybridization with Runx2- and Runx3-specific probes. Both genes were coexpressed in cartilaginous condensations, indicating a cooperative role in the regulation of early chondrocyte differentiation and thus explaining the expansion/maintenance of cartilage in the carpus and joints of infected chick limbs.
(c)2002 Elsevier Science (USA).
Similar articles
- The distinct role of the Runx proteins in chondrocyte differentiation and intervertebral disc degeneration: findings in murine models and in human disease.
Sato S, Kimura A, Ozdemir J, Asou Y, Miyazaki M, Jinno T, Ae K, Liu X, Osaki M, Takeuchi Y, Fukumoto S, Kawaguchi H, Haro H, Shinomiya K, Karsenty G, Takeda S. Sato S, et al. Arthritis Rheum. 2008 Sep;58(9):2764-75. doi: 10.1002/art.23805. Arthritis Rheum. 2008. PMID: 18759297 - Runx1/AML1/Cbfa2 mediates onset of mesenchymal cell differentiation toward chondrogenesis.
Wang Y, Belflower RM, Dong YF, Schwarz EM, O'Keefe RJ, Drissi H. Wang Y, et al. J Bone Miner Res. 2005 Sep;20(9):1624-36. doi: 10.1359/JBMR.050516. Epub 2005 May 23. J Bone Miner Res. 2005. PMID: 16059634 - Cbfbeta interacts with Runx2 and has a critical role in bone development.
Kundu M, Javed A, Jeon JP, Horner A, Shum L, Eckhaus M, Muenke M, Lian JB, Yang Y, Nuckolls GH, Stein GS, Liu PP. Kundu M, et al. Nat Genet. 2002 Dec;32(4):639-44. doi: 10.1038/ng1050. Epub 2002 Nov 18. Nat Genet. 2002. PMID: 12434156 - Requisite roles of Runx2 and Cbfb in skeletal development.
Komori T. Komori T. J Bone Miner Metab. 2003;21(4):193-7. doi: 10.1007/s00774-002-0408-0. J Bone Miner Metab. 2003. PMID: 12811622 Review. - Runx2, a multifunctional transcription factor in skeletal development.
Komori T. Komori T. J Cell Biochem. 2002;87(1):1-8. doi: 10.1002/jcb.10276. J Cell Biochem. 2002. PMID: 12210716 Review.
Cited by
- Regulation of Skeletal Development and Maintenance by Runx2 and Sp7.
Komori T. Komori T. Int J Mol Sci. 2024 Sep 20;25(18):10102. doi: 10.3390/ijms251810102. Int J Mol Sci. 2024. PMID: 39337587 Free PMC article. Review. - Exosomes Derived from Runx2-Overexpressing BMSCs Enhance Cartilage Tissue Regeneration and Prevent Osteoarthritis of the Knee in a Rabbit Model.
Hu J, Shi ZS, Liu XZ, Cai HT, Yang AF, Sun DM, Xu LL, Yang Y, Li ZH. Hu J, et al. Stem Cells Int. 2022 Nov 28;2022:6865041. doi: 10.1155/2022/6865041. eCollection 2022. Stem Cells Int. 2022. PMID: 39282499 Free PMC article. - A synthetic, closed-looped gene circuit for the autonomous regulation of RUNX2 activity during chondrogenesis.
Kaur G, Wu B, Murali S, Lanigan T, Coleman RM. Kaur G, et al. FASEB J. 2024 Feb 29;38(4):e23484. doi: 10.1096/fj.202300348RR. FASEB J. 2024. PMID: 38407380 - The role and mechanism of biological collagen membranes in repairing cartilage injury through the p38MAPK signaling pathway.
Yuan LB, Jin T, Yao L, Yin DH, Xu YQ. Yuan LB, et al. J Orthop Surg Res. 2023 Nov 6;18(1):837. doi: 10.1186/s13018-023-04261-y. J Orthop Surg Res. 2023. PMID: 37932780 Free PMC article. - Chondrocyte Homeostasis and Differentiation: Transcriptional Control and Signaling in Healthy and Osteoarthritic Conditions.
Michelacci YM, Baccarin RYA, Rodrigues NNP. Michelacci YM, et al. Life (Basel). 2023 Jun 28;13(7):1460. doi: 10.3390/life13071460. Life (Basel). 2023. PMID: 37511835 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases