Differentiated activities of decorin and biglycan in the progression of post-traumatic osteoarthritis.

OBJECTIVE: To delineate the activities of decorin and biglycan in the progression of post-traumatic osteoarthritis (PTOA). DESIGN: Three-month-old inducible biglycan (Bgn(iKO)) and decorin/biglycan compound (Dcn/Bgn(iKO)) knockout mice were subjected to the destabilization of the medial meniscus (DMM) surgery to induce PTOA. The OA phenotype was evaluated by assessing joint structure and sulfated glycosaminoglycan (sGAG) staining via histology, surface collagen fibril nanostructure and calcium content via scanning electron microscopy, tissue modulus via atomic force microscopy-nanoindentation, as well as subchondral bone structure and meniscus ossification via micro-computed tomography. Outcomes were compared with previous findings in the inducible decorin (Dcn(iKO)) knockout mice. RESULTS: In the DMM model, Bgn(iKO) mice developed similar degree of OA as the control (0.44 [-0.18 1.05] difference in modified Mankin score), different from the more severe OA phenotype observed in Dcn(iKO) mice (1.38 [0.91 1.85] difference). Dcn/Bgn(iKO) mice exhibited similar histological OA phenotype as Dcn(iKO) mice (1.51 [0.97 2.04] difference vs control), including aggravated loss of sGAGs, salient surface fibrillation and formation of osteophyte. Meanwhile, Dcn/Bgn(iKO) mice showed further cartilage thinning than Dcn(iKO) mice, resulting in the exposure of underlying calcified tissues and aberrantly high surface modulus. Bgn(iKO) and Dcn/Bgn(iKO) mice developed altered subchondral trabecular bone structure in both Sham and DMM groups, while Dcn(iKO) and control mice did not. CONCLUSION: In PTOA, decorin plays a more crucial role than biglycan in regulating cartilage degeneration, while biglycan is more important in regulating subchondral bone structure. The two have distinct activities and modest synergy in the pathogenesis of PTOA.