title: BMPRIA mediated signaling is essential for temporomandibular joint development in mice.
abstract: The central importance of BMP signaling in the development and homeostasis of synovial joint of appendicular skeleton has been well documented, but its role in the development of temporomandibular joint (TMJ), also classified as a synovial joint, remains completely unknown. In this study, we investigated the function of BMPRIA mediated signaling in TMJ development in mice by transgenic loss-of- and gain-of-function approaches. We found that BMPRIA is expressed in the cranial neural crest (CNC)-derived developing condyle and glenoid fossa, major components of TMJ, as well as the interzone mesenchymal cells. Wnt1-Cre mediated tissue specific inactivation of BmprIa in CNC lineage led to defective TMJ development, including failure of articular disc separation from a hypoplastic condyle, persistence of interzone cells, and failed formation of a functional fibrocartilage layer on the articular surface of the glenoid fossa and condyle, which could be at least partially attributed to the down-regulation of Ihh in the developing condyle and inhibition of apoptosis in the interzone. On the other hand, augmented BMPRIA signaling by Wnt1-Cre driven expression of a constitutively active form of BmprIa (caBmprIa) inhibited osteogenesis of the glenoid fossa and converted the condylar primordium from secondary cartilage to primary cartilage associated with ectopic activation of Smad-dependent pathway but inhibition of JNK pathway, leading to TMJ agenesis. Our results present unambiguous evidence for an essential role of finely tuned BMPRIA mediated signaling in TMJ development.
authors.affiliation: Department of Cell and Molecular Biology, Tulane University, New Orleans, Louisiana, United States of America.
authors.forename: Shuping
authors.initials: S
authors.lastname: Gu
authors.affiliation: Department of Cell and Molecular Biology, Tulane University, New Orleans, Louisiana, United States of America; Department of Dentistry, ZhongShan Hospital, FuDan University, Shanghai, P.R. China.
authors.forename: Weijie
authors.initials: W
authors.lastname: Wu
authors.affiliation: Department of Cell and Molecular Biology, Tulane University, New Orleans, Louisiana, United States of America.
authors.forename: Chao
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Cell and Molecular Biology, Tulane University, New Orleans, Louisiana, United States of America; Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China.
authors.forename: Ling
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Cell and Molecular Biology, Tulane University, New Orleans, Louisiana, United States of America.
authors.forename: Cheng
authors.initials: C
authors.lastname: Sun
authors.affiliation: Department of Cell and Molecular Biology, Tulane University, New Orleans, Louisiana, United States of America.
authors.forename: Wenduo
authors.initials: W
authors.lastname: Ye
authors.affiliation: Department of Cell and Molecular Biology, Tulane University, New Orleans, Louisiana, United States of America; Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, P.R. China.
authors.forename: Xihai
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, United States of America.
authors.forename: Jianquan
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, United States of America.
authors.forename: Fanxin
authors.initials: F
authors.lastname: Long
authors.affiliation: Department of Cell and Molecular Biology, Tulane University, New Orleans, Louisiana, United States of America.
authors.forename: YiPing
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000235:genetics / Q000502:physiology*; D019902:Chondrocytes / Q000502:physiology; D020219:Chondrogenesis / Q000235:genetics; D004622:Embryo, Mammalian; D005260:Female; D051379:Mice; D008822:Mice, Transgenic; D009432:Neural Crest / Q000196:embryology / Q000378:metabolism; D011247:Pregnancy; D015398:Signal Transduction / Q000235:genetics; D013704:Temporomandibular Joint / Q000196:embryology*
chemical_list: C498212:Bmpr1a protein, mouse; D052005:Bone Morphogenetic Protein Receptors, Type I
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