siMMP13-μPLs enable sustained in vivo inhibition of MMP13 and reduction of inflammatory gene expression in the total joint and synovium. (A and B) MMP13 gene expression in (A) combined cartilage and synovium and (B) medial synovial tissue alone over time after a single siMMP13-μPL treatment in mouse PTOA model. (C) MMP13 immunohistochemistry in the cartilage, synovial, and meniscal tissues at day 28 of loading after a single siMMP13-μPL treatment. (D and E) qRT-PCR measurement of expression of C1s, C2, IL-1β, IL-6, and TNFα in (D) the combined total joint lateral synovial and cartilage tissues and (E) medial synovial tissues. Normalization of expression for each gene was done to similar joint tissues harvested at day 28 from animals treated with siNEG-μPLs. *, p < 0.05; **, p < 0.01, compared to siNEG μPLs; all error bars represent standard error of the mean.