Expressing human SHOX in Shox2(SHOX KI)/(KI) mice leads to congenital osteoarthritis-like disease of the temporomandibular joint in postnatal mice

The temporomandibular joint (TMJ), a unique synovial joint whose development differs from that of other synovial joints, develops from two distinct mesenchymal condensations that grow toward each other and ossify through different mechanisms. The short stature homeobox 2 (Shox2) gene serves an important role in TMJ development and previous studies have demonstrated that Shox2(SHOX KI)/(KI) mice display a TMJ defective phenotype, congenital dysplasia and premature eroding of the articular disc, which is clinically defined as a TMJ disorder. In the present study, Shox2(SHOX KI)/(KI) mouse models were used to investigate the mechanisms of congenital osteoarthritis (OA)-like disease during postnatal TMJ growth. Shox2(SHOX KI)/(KI) mice were observed to develop a severe muscle wasting syndrome from day 7 postnatal. Histological examination indicated that the condyle and glenoid fossa of Shox2(SHOX KI)/(KI) mice was reduced in size in the second week after birth. The condyles of Shox2(SHOX KI)/(KI) mice exhibited reduced expression levels of collagen type II and Indian hedgehog, and increased expression of collagen type I. A marked increase in matrix metalloproteinase 9 (MMP9) and MMP13 in the condyles was also observed. These cellular and molecular defects may contribute to the observed (OA)-like phenotype of Shox2(SHOX KI)/(KI) mouse TMJs.