title: Overexpression of Indian hedgehog partially rescues short stature homeobox 2-overexpression-associated congenital dysplasia of the temporomandibular joint in mice.
abstract: The role of short stature homeobox 2 (shox2) in the development and homeostasis of the temporomandibular joint (TMJ) has been well documented. Shox2 is known to be expressed in the progenitor cells and perichondrium of the developing condyle. A previous study by our group reported that overexpression of shox2 leads to congenital dysplasia of the TMJ via downregulation of the Indian hedgehog (Ihh) signaling pathway, which is essential for embryonic disc primordium formation and mandibular condylar growth. To determine whether overexpression of Ihh may rescue the overexpression of shox2 leading to congenital dysplasia of the TMJ, a mouse model in which Ihh and shox2 were overexpressed (Wnt1-Cre; pMes-stop shox2; pMes-stop Ihh mice) was utilized to assess the consequences of this overexpression on TMJ development during post-natal life. The results showed that the developmental process and expression levels of runt-related transcription factor 2 and sex determining region Y-box 9 in the TMJ of the Wnt1-Cre; pMes-stop shox2; pMes-stop Ihh mice were similar to those in wild‑type mice. Overexpression of Ihh rescued shox2 overexpression-associated reduction of extracellular matrix components. However, overexpression of Ihh did not inhibit the shox2 overexpression-associated increase of matrix metalloproteinases (MMPs) MMP9, MMP13 and apoptosis in the TMJ. These combinatory cellular and molecular defects appeared to account for the observed congenital dysplasia of TMJ, suggesting that overexpression of Ihh partially rescued shox2 overexpression‑associated congenital dysplasia of the TMJ in mice.
authors.affiliation: Institute of Bone Diseases, Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
authors.forename: Xihai
authors.initials: X
authors.lastname: Li
authors.affiliation: Research Base of Traditional Chinese Medicine Syndrome, College of Traditional Chinese Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
authors.forename: Wenna
authors.initials: W
authors.lastname: Liang
authors.affiliation: Institute of Bone Diseases, Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
authors.forename: Hongzhi
authors.initials: H
authors.lastname: Ye
authors.affiliation: Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
authors.forename: Xiaping
authors.initials: X
authors.lastname: Weng
authors.affiliation: Institute of Bone Diseases, Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
authors.forename: Fayuan
authors.initials: F
authors.lastname: Liu
authors.affiliation: Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
authors.forename: Pingdong
authors.initials: P
authors.lastname: Lin
authors.affiliation: Institute of Bone Diseases, Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
authors.forename: Xianxiang
authors.initials: X
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis; D001848:Bone Diseases, Developmental / Q000151:congenital / Q000378:metabolism / Q000473:pathology*; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D061165:Glenoid Cavity / Q000378:metabolism; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D055758:SOX9 Transcription Factor / Q000378:metabolism; D013705:Temporomandibular Joint Disorders / Q000151:congenital / Q000378:metabolism / Q000473:pathology*; D015854:Up-Regulation
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; C493716:Runx2 protein, mouse; D055758:SOX9 Transcription Factor; C484663:Shox2 protein, mouse; C527933:Sox9 protein, mouse; C514061:ihh protein, mouse; D053509:Matrix Metalloproteinase 13; D020780:Matrix Metalloproteinase 9