Notably, sustained rAAV production of TGF-β in OA cartilage advantageously reduced the expression of key OA-associated markers of chondrocyte hypertrophic and terminal differentiation (type-X collagen, MMP-13, PTHrP, β-catenin) while increasing that of protective TIMPs and of the TGF-β receptor I in a manner that restored a favorable ALK1/ALK5 balance.
In aging cartilage and experimental OA, the ratio ALK1/ALK5 has been found to be increased, and the expression of ALK1 is correlated with matrix metalloproteinase-13 expression.