Abstract
The temporomandibular joint (TMJ) consists in the glenoid fossa arising from the otic capsule through intramembranous ossification, the fibrocartilaginous disc and the condyle, which is derived from the secondary cartilage by endochondral ossification. We have reported previously that cranial neural-crest-specific inactivation of the homeobox gene Shox2, which is expressed in the mesenchymal cells of the maxilla-mandibular junction and later in the progenitor cells and perichondrium of the developing chondyle, leads to dysplasia and ankylosis of the TMJ and that replacement of the mouse Shox2 with the human SHOX gene rescues the dysplastic and ankylosis phenotypes but results in a prematurely worn out articular disc. In this study, we investigate the molecular and cellular bases for the prematurely worn out articular disc in the TMJ of mice carrying the human SHOX replacement allele in the Shox2 locus (termed Shox2 SHOX-KI/KI). We find that the developmental process and expression of several key genes in the TMJ of Shox2 SHOX-KI/KI mice are similar to that of controls. However, the disc of the Shox2 SHOX-KI/KI TMJ exhibits a reduced level of Collagen I and Aggrecan, accompanied by increased activities of matrix metalloproteinases and a down-regulation of Ihh expression. Dramatically increased cell apoptosis in the disc was also observed. These combinatory cellular and molecular defects appear to contribute to the observed disc phenotype, suggesting that, although human SHOX can exert similar functions to mouse Shox2 in regulating early TMJ development, it apparently has a distinct function in the regulation of those molecules that are involved in tissue homeostasis.
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X.L. received a fellowship from the Fujian University of Traditional Chinese Medicine, Fujian, P.R. China. Y.Z. was supported by a fellowship from the Department of Health, Fujian Province, P.R. China. Financial support for this study was provided by an NIH grant (R01 DE17792) to Y.P.C.
The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article.
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Li, X., Liu, H., Gu, S. et al. Replacing Shox2 with human SHOX leads to congenital disc degeneration of the temporomandibular joint in mice. Cell Tissue Res 355, 345–354 (2014). https://doi.org/10.1007/s00441-013-1743-2
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DOI: https://doi.org/10.1007/s00441-013-1743-2