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Background: Recent studies have evidenced that higher adiposity in infrapatellar fat pad(IFP)induce inflammatory phenotype in the knee-joint and thereby contribute to development and progression of osteoarthritis(OA).In particular,IFP adipocytes–derived inflammatory cytokines participate in pathologic events.Our previous research has already addressed the therapeutic efficacy of hyaluronic acid and platelet-rich plasma(HA+PRP),including the promotion of cartilage regeneration and the inhibition of inflammation.Current study aimed to explore remedial action of co-administered HA+PRP in osteoarthritic recovery via IFP-adipocytes inhibition.Hypothesis: HA+PRP repairs OA articular cartilage through inhibiting the release of adipokines from IFP-Adipocytes.Study design: Controlled laboratory study.Methods: IFP-adipocytes and articular chondrocytes were obtained from 10 OA patients.Effects of releasate containing cytokines and adipokines in IFP adipocyte-derived conditioned medium(IACM)on articular chondrocytes and IFP-adipocytes itself were evaluated.Therapeutic efficacy of exogenous HA+PRP was determined through their administration to co-cultured IFP-adipocytes and articular chondrocytes and further demonstrated in 3D arthritic neo-cartilage model.Results: IACM and IFP-adipocytes–induced microenvironment could induce de-differentiated and inflammatory phenotypes in articular chondrocytes.HA+PRP decreased inflammatory potential of IFP-adipocytes through profound inhibition of cytokines and adipokines.IACM-mediated reduced cartilaginous extracellular matrix(ECM)could also be recovered through HA+PRP in 3D arthritic neo-cartilage model.Conclusions: IFP-Adipocytes-derived releasates mediated inflammatory response de-differentiation in chondrocytes which was recovered through HA+PRP administration.Clinical Relevance: Our findings demonstrated that HA+PRP effectively diminished IFP-adipocytes-promoted inflammation in articular chondrocytes which indicates that IFP could be a potential therapeutic target for OA therapy.