title: Lubricin protects the temporomandibular joint surfaces from degeneration.
abstract: The temporomandibular joint (TMJ) is a specialized synovial joint essential for the mobility and function of the mammalian jaw. The TMJ is composed of the mandibular condyle, the glenoid fossa of the temporal bone, and a fibrocartilagenous disc interposed between these bones. A fibrous capsule, lined on the luminal surface by the synovial membrane, links these bones and retains synovial fluid within the cavity. The major component of synovial fluid is lubricin, a glycoprotein encoded by the gene proteoglycan 4 (Prg4), which is synthesized by chondrocytes at the surface of the articular cartilage and by synovial lining cells. We previously showed that in the knee joint, Prg4 is crucial for maintenance of cartilage surfaces and for regulating proliferation of the intimal cells in the synovium. Consequently, the objective of this study was to determine the role of lubricin in the maintenance of the TMJ. We found that mice lacking lubricin have a normal TMJ at birth, but develop degeneration resembling TMJ osteoarthritis by 2 months, increasing in severity over time. Disease progression in Prg4-/- mice results in synovial hyperplasia, deterioration of cartilage in the condyle, disc and fossa with an increase in chondrocyte number and their redistribution in clusters with loss of superficial zone chondrocytes. All articular surfaces of the joint had a prominent layer of protein deposition. Compared to the knee joint, the osteoarthritis-like phenotype was more severe and manifested earlier in the TMJ. Taken together, the lack of lubricin in the TMJ causes osteoarthritis-like degeneration that affects the articular cartilage as well as the integrity of multiple joint tissues. Our results provide the first molecular evidence of the role of lubricin in the TMJ and suggest that Prg4-/- mice might provide a valuable new animal model for the study of the early events of TMJ osteoarthritis.
authors.affiliation: Department of Orthopaedic Surgery, Boston Children's Hospital, Boston, Massachusetts, United States of America; Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Adele
authors.initials: A
authors.lastname: Hill
authors.affiliation: Department of Plastic and Oral Surgery, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Juanita
authors.initials: J
authors.lastname: Duran
authors.affiliation: Department of Plastic and Oral Surgery, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Patricia
authors.initials: P
authors.lastname: Purcell
mesh_terms: D000818:Animals; D005260:Female; D006023:Glycoproteins / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism; D013704:Temporomandibular Joint / Q000378:metabolism* / Q000473:pathology*; D013705:Temporomandibular Joint Disorders / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000099158:Proteoglycan 4
chemical_list: D006023:Glycoproteins; D011509:Proteoglycans; D000099158:Proteoglycan 4; C498837:Prg4 protein, mouse