A disease-risk mutation in COL6A3 alters the biologic response of chondrocytes to hyper-physiologic mechanical loading

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Purpose: We set out to determine the interacting effect of a high-impact osteoarthritis mutation in COL6A3 and hyper-physiologic mechanical stress on chondrocyte signaling. Hereto, we differentiated wild-type and COL6A3-mutated human induced pluripotent stem cells (hiPSCs) with an established 3D, in vitro chondrogenesis protocol. We hypothesized that the amino-acid change in the von Willebrand factor 8 of COL6A3 affects cartilage integrity by an aberrant mechanobiologic response of chondrocytes, particularly under hyper-physiologic mechanical stress.