Molecular Consequences of <em>CCN6</em> Variants Encoding WISP3 in Progressive Pseudorheumatoid Dysplasia

Progressive pseudorheumatoid dysplasia (PPD) is a rare autosomal recessive cartilage disorder caused by biallelic variants in CCN6, which encodes the matricellular protein WISP3. Although WISP3 is thought to contribute to extracellular matrix (ECM) homeostasis, its precise molecular role in PPD remains unclear. To elucidate how disease-associated CCN6 variants affect chondrocyte function, we overexpressed four variants-p.Cys52*, p.Tyr109*, p.Gly83Glu, and p.Cys114Trp-all located within the IGFBP...