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Moderate forced running exercise induces cartilage adaptation but exacerbates the molecular cartilage phenotype of type IX collagen knock-out mice
Journal article   Open access   Peer reviewed

Moderate forced running exercise induces cartilage adaptation but exacerbates the molecular cartilage phenotype of type IX collagen knock-out mice

Miriam Weyers, Thomas Li, Maren Dreiner, Daniela Mählich, Charlotte Lorenz, Luisa de Roy, Paola Zigrino, Lin Han, Bent Brachvogel, Frank Zaucke, …
American Journal of Physiology: Cell Physiology, Forthcoming
19 May 2026
DOI: https://doi.org/10.1152/ajpcell.00959.2025
PMID: 42154996
Featured in Collection :   Drexel's Newest Publications
url
https://doi.org/10.1152/ajpcell.00959.2025View
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Abstract

articular cartilage running exercise type IX collagen growth plate Extracellular Matrix
Mechanical loading is essential for the assembly and maintenance of the articular cartilage extracellular matrix (ECM), while 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 six weeks (20% incline, 18 m/min, 40 min/day, five days/week). 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, non-degenerative 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.

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