Lubricin, encoded by the Prg4 gene, is abundantly expressed by superficial zone (SFZ) cells and synoviocytes, and is essential in joint surface lubrication. Human temporomandibular joint osteoarthritis (TMJ-OA) is the most common degenerative joint disease of the TMJ. Host adaptive factors, trauma, and mechanical stress (MS) factors may play a role in its etiology. Herein, we investigated the mechanism by which lubricin regulates TMJ homeostasis.
We first employed a MS mouse model with a metal plate on the maxillary anterior teeth and a surgical articular disc displacement (ADD) mouse model to reproduce malocclusion and inflammation of the TMJ, respectively. To investigate the role of lubricin in TMJ homeostasis, we used heterozygous Prg4-CreERT2 mice, whereby the CreERT2 cassette was knocked into the Prg4 translation initiation site, producing Prg4 heteroknockout (HT) mice. In Prg4 HT mice, the number of SFZ cells in the TMJ was lower than that in WT mice, and fibrosis and unlayered columnar chondrocytes were observed in Prg4 HT mice at 8-weeks-old.
When we induced MS and ADD in Prg4 HT mice at 8-weeks-old, 2 weeks after induction, synovial hyperplasia of the posterior synovium in the articular disc was observed in the MS model, whereas severe deformity of the mandibular condyle and hyperplasia of the hypertrophic chondrocyte layer extending posteriorly to the subchondral bone were observed in the ADD model. In in vitro experiments, primary fibroblastic and synovium cells from the articular discs of Prg4 HT and WT mice were cultured and treated with interleukin (IL)-1β under hypoxia conditions, and then were analyzed by RT-PCR. IL-1β-induced inflammation markers enhancement was increased in the primary cells of Prg4 HT mice compared to those of the WT mice.
Thus, lubricin in TMJ facilitates inflammatory stimuli suppression, suggesting that it may be a promising target for TMJ-OA treatment.