Induction of MMP-13 by hyaluronan oligosaccharide in temporomandibular joint chondrocytes

Objectives: Temporomandibular joint (TMJ) condyles contain articular cartilage that is similar to the articular cartilage of extremities, and often undergoes similar degenerative changes such as those associated with osteoarthritis (OA). Degenerative products of cartilage matrix often induce catabolic states in chondrocytes and could thus serve as continually-generated enhancers of the pathological process. Hyaluronan, a major glycosaminoglycan in cartilage is also becomes fragmented during OA, and changes in hyaluronan size are thought to contribute to TMJ disorders due to the loss of synovial fluid lubrication. Moreover, fragmented hyaluronan may directly act on chondrocytes through the hyaluronan receptor CD44 as it does in other cell systems. However, little information is known concerning the effects of low molecular weight hyaluronan on catabolic action chondrocytes of TMJ articular cartilage (TAC). This study was conducted to clarify the effects of hyaluronan oligosaccharide on MMP-13 expression in TAC. Methods: We used high density primary cultures of chondrocytes derived from bovine TMJ, and examined the effects of hyaluronan oligosaccharides on the expression and activity of matrix metalloproteinase-13 (MMP-13) by Real time RT-PCR and casein zymography assay, respectively. Results: The expressions of type II collagen, aggrecan and HAS-2 mRNAs were lower in TAC compared to articular chondrocytes from metacarpophalangeal joints (MAC). On the other hand, the expression of type I collagen and CD44 is higher in TAC. Addition of exogenous hyaluronan oligosaccharide induced the expression of MMP-13 mRNA in both TAC and MAC. Furthermore, casein zymography in conditioned medium showed the increase in the activity of an ~50 kDa protein. Conclusion: These results suggest that TAC express abundant CD44 and, that low molecular weight hyaluronan activates TAC resulting in a substantial enhancement of MMP-13. Increases in such catabolic activities may contribute to drive the TMJ OA phenotype long after the initiating events which are no longer present.