Lubricin is Required for the Structural Integrity and Post-natal Maintenance of TMJ

Abstract

The Proteoglycan 4 (Prg4) product lubricin plays essential roles in boundary lubrication and movement in limb synovial joints, but its roles in temporomandibular joint (TMJ) are unclear. Thus, we characterized the TMJ phenotype in wild-type and Prg4 -/-mouse littermates over age. As early as 2 weeks of age, mutant mice exhibited hyperplasia in the glenoid fossa articular cartilage, articular disc, and synovial membrane. By 1 month of age, there were fewer condylar superficial tenascin-C/ Col1-positive cells and more numerous apoptotic condylar apical cells, while chondroprogenitors displayed higher mitotic activity, and Sox9-, Col2-, and ColX-expressing chondrocyte zones were significantly expanded. Mutant subchondral bone contained numerous Catepsin K-expressing osteoclasts at the chondro-osseous junction, increased invasive marrow cavities, and suboptimal subchondral bone. Mutant glenoid fossa, disc, synovial cells, and condyles displayed higher Hyaluronan synthase 2 expression. Mutant discs also lost their characteristic concave shape, exhibited ectopic chondrocyte differentiation, and occasionally adhered to condylar surfaces. A fibrinoid substance of unclear origin often covered the condylar surface. By 6 months of age, mutant condyles displayed osteoarthritic degradation with apical/mid-zone separation. In sum, lubricin exerts multiple essential direct and indirect roles to preserve TMJ structural and cellular integrity over post-natal life.

Confocal imaging of mouse mandibular condyle cartilage

“…It has previously been reported, using standard histology, that lubricin knockout mice develop age-related abnormalities in their TMJs, including widening and flattening of condylar surface with superficial chondrocyte loss189. Our confocal imaging detected these same changes in Prg4 knockout mice without requiring decalcification, paraffin embedding, sectioning, and staining (Fig.…”

Osteophyte formation and matrix mineralization in a TMJ osteoarthritis mouse model are associated with ectopic hedgehog signaling

“…Notably, Prg4- null mice also displayed characteristic features of degenerative changes in TMJs including articular surface deterioration, loss of disc concave-convex morphology, synovial membrane hyperplasia and protein deposition. (Hill et al, 2014; Koyama et al, 2014). We also reported that Prg4 -null mice displayed increased levels of chondrogenesis and ectopic cartilage formation within TMJ components (Bechtold et al, 2015; Koyama et al, 2014), but the cellular, signaling and molecular mechanisms underling such potentially important pathogenic transformation remains unclear.…”

The distribution of superficial zone protein (SZP)/lubricin/PRG4 and boundary mode frictional properties of the bovine diarthrodial joint

“…While the majority of SZP in the knee joint is synthesized by the superficial zone articular cartilage and synovium (Schumacher et al, 1999), cells in the meniscus (Schumacher et al, 2005), tendon (Rees et al, 2002), ligament (Lee et al, 2008b; Zhang et al, 2011), and infrapatellar fat pad (Lee et al, 2008a) produce SZP as well. SZP has also been demonstrated to be expressed by, and lubricate, the eye lid-corneal interface (Cheriyan et al, 2011; Schmidt et al, 2013), intervertebral disc (Shine et al, 2009), and temporomandibular joint (TMJ) (Koyama et al, 2014; Wei et al, 2010). While the source is unknown, SZP is additionally present in whole blood, plasma, serum, and platelet-rich plasma (Sakata et al, 2015; Su et al, 2001).…”