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.
Highlights
As an evolutionary creature, the temporomandibular joint (TMJ) is a unique synovial joint generated only in mammals and is involved in food capture and intake, speech, as well as maturation of the facial contour [1]
Inactivation of BmprIa in cranial neural crest (CNC) lineage leads to defective TMJ formation To investigate the role of BmprIa in TMJ development, we began with examination of BMPRIA expression by immunohistochemistry
We present evidence that BMPRIA mediated signaling is essential for TMJ morphogenesis, and overly activated BMPRIA signaling is detrimental to TMJ formation
Summary
The temporomandibular joint (TMJ) is a unique synovial joint generated only in mammals and is involved in food capture and intake, speech, as well as maturation of the facial contour [1] It is made of specific components originated from the skull base and the low jaw including the glenoid fossa, condyle, articular disc, ligaments, and joint capsule. The TMJ develops from two distinct mesenchymal condensations, the glenoid fossa blastema that ossifies primarily through intramembranous bone formation, and the condylar blastema that undergoes endochondral ossification These two primordia are initially separated widely by intervening mesenchyme that was thought to later contribute to the articular disc and capsule, as well as the synovial lining of joint cavity [3,4] Subsequently, the condylar primordium, arising from the periosteum of the mandibular bone and classified as secondary cartilage [5,6], grows rapidly towards the glenoid fossa, and the articular disc forming from a condensed stripe flanking the apex of the condyle and subsequently separating from the latter, divides the interzone into the upper and lower joint cavities [7]. This intricate multi-step developmental process is regulated by intrinsic and extrinsic factors
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