Moderate forced running exercise induces cartilage adaptation but exacerbates the molecular cartilage phenotype of type IX collagen knockout mice.

Mechanical loading is essential for the assembly and maintenance of the articular cartilage extracellular matrix (ECM), whereas alterations in ECM composition profoundly affect cartilage mechanics and function. Type IX collagen is a heterotrimeric fibril-associated collagen with interrupted triple helices (FACIT) that is covalently linked to type II collagen. It restricts lateral fibril growth and mediates interactions with other ECM components. Although type IX collagen expression is mechanosensitive and implicated in cartilage mechanotransduction, its precise functional role is not yet fully understood. This study investigated the combined effects of type IX collagen deficiency and moderate mechanical loading on articular and growth plate cartilage. Twelve-week-old female wild-type (WT) and Col9a1-/- mice were randomly assigned to control (CON) or forced running exercise (EXE) groups (n = 10-12 per group). EXE animals underwent treadmill training for 6 wk (20% incline, 18 m/min, 40 min/day, 5 days/wk). Type IX collagen deficiency resulted in an abnormal growth plate architecture and a reduction of all matrilins and cartilage oligomeric matrix protein (COMP) in articular cartilage. Moderate forced running exercise induced a significant increase (P < 0.05) in cartilage thickness at the lateral femoral condyle and altered ECM composition in Col9a1-/- mice, without evidence of cartilage degeneration. WT mice showed no comparable structural changes. In conclusion, moderate mechanical loading elicits localized, nondegenerative, structural and molecular adaptations in articular cartilage and only modestly modulates the cartilage phenotype associated with type IX collagen deficiency. These findings suggest a limited, yet context-dependent role of type IX collagen in cartilage mechanoadaptation.NEW & NOTEWORTHY Moderate forced running exercise only slightly enhances the cartilage phenotype in aging female type IX collagen knockout mice and induces local, nondegenerative, structural and molecular adaptations in the articular cartilage ECM. Alterations in the cartilage phenotype do not depend on the age of the mice.