Inflammation-inducible Strategies for Growth Factor Gene Therapy to Promote Joint Tissue Repair: Applications for Osteoarthritis Therapy

Rationale: Osteoarthritis (OA) features cartilage loss, bone remodeling, and chronic inflammation. Dysregulated transforming growth factor beta-1 (TGF-β1) in OA and its constitutive overexpression risks unwanted tissue growth. We aimed to develop an inflammation-inducible TGF-β1 delivery system using cell culture models. Hypothesis: An inducible promoter will provide controlled, context-dependent Tgfb1 expression with fewer adverse effects than a constitutive promoter. Methods: We cloned Tgfb1 with either endothelial leukocyte adhesion molecule-1 (Elam1) inducible promoter or elongation factor 1-alpha (Ef1a) constitutive promoter into plasmids, transfected them into C3H10T1/2 cells, and assessed Tgfb1 expression using qPCR. Expression downstream of Ef1a was sustained while expression downstream of Elam1 was induced by lipopolysaccharide (LPS). Results: Ef1a drove robust Tgfb1 expression, but the Elam1 failed to drive expression in response to LPS in this cell line. Conclusion: Ef1a promoter effectively drives constitutive Tgfb1 overexpression in C3H10T1/2 cells; further Elam1 studies are required. Significance: This work supports the potential for inflammation-inducible TGF-β1 expression to protect chondrocytes in OA, guiding future in-vivo studies.