Poster 2: Cell and Tissue Studies

Joohyun Lim

University of Delaware

Temporomandibular disorders (TMDs) derive from abnormalities in the temporomandibular joint (TMJ) and adjacent connective tissues that cause severe orofacial pain and reduced range of motion. Here, we report a murine model of osteogenesis imperfecta (OI) which displays aberrant bone formation in the tendon-bone interface (TBI) of TMJ due to defects in the posttranslational modification and cross-linking of collagen I. Loss-of-function mutations in FKBP10 causes OI with joint contracture. In addition, we recently reported that tendon-specific deletion of Fkbp10 causes postnatal joint deformities and impaired locomotor function which corroborates the phenotypic spectrum observed in patients. Interestingly, conditional deletion of Fkbp10 also induced abnormal ossification in TMJ that increases mandibular condyle length and width at 6 and 18 months-of-age, despite normal mandibular development. The ectopic bone formation in TMJ of Fkbp10-deficient mice was triggered by ectopic bone growth in the TBI at 1.5 months-of-age. Interestingly, abnormal bone growth in Fkbp10 mutants coincided with a significant increase in ?SMA-expressing cell populations in the TBI. Thus, Fkbp10 is likely required for preventing abnormal differentiation of this cell population. Collectively, the data suggests that posttranslational modification of the collagen matrix is critical for postnatal tissue homeostasis of the TMJ, in part through regulating a unique population of cells in the TBI.

Research Area: Skeletal Disorder & Treatments