title: Synergistic anabolic actions of hyaluronic acid and platelet-rich plasma on cartilage regeneration in osteoarthritis therapy.
abstract: Osteoarthritis (OA) is a common disease associated with tissue inflammation, physical disability and imbalanced homeostasis in cartilage. For advanced treatments, biological approaches are currently focused on tissue regeneration and anti-inflammation. This study was undertaken to evaluate the therapeutic efficacies of hyaluronic acid (HA) and platelet-rich plasma (PRP) (HA+PRP) on OA. Articular chondrocytes were obtained from five OA patients. The optimal HA and PRP concentrations were evaluated by MTT assay. The expressions of chondrogenic and inflammatory genes were analyzed by RT-PCR. Signaling pathway was examined by immunoblotting and the expressions of OA pathology-related chemokines and cytokines was demonstrated by real-time PCR-based SuperArray. The therapeutic efficacies of HA+PRP were then demonstrated in 3D arthritic neo-cartilage and ACLT-OA model. Here we showed that HA+PRP could greatly retrieve pro-inflammatory cytokines-reduced articular chondrocytes proliferation and chondrogenic phenotypes, the mechanism of which involve the sequential activation of specific receptors CD44 and TGF-βRII, downstream mediators Smad2/3 and Erk1/2, and the chondrogenic transcription factor SOX9. The real-time PCR-based SuperArray results also indicated that OA pathology-related chemokines and cytokines could be efficiently suppressed by HA+PRP. Moreover, the cartilaginous ECM could be retrieved from inflammation-induced degradation by HA+PRP in both 2D monolayer and 3D neo-cartilage model. Finally, the intra-articular injection of HA+PRP could strongly rescue the meniscus tear and cartilage breakdown and then decrease OA-related immune cells. The combination of HA+PRP can synergistically promote cartilage regeneration and inhibit OA inflammation. This study might offer an advanced and alternative OA treatment based on detailed regenerative mechanisms.
authors.affiliation: Stem Cell Research Center, Taipei Medical University, Taipei, Taiwan; Graduate Institute of Biomedical Materials and Engineering, College of Oral, Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Wei-Hong
authors.initials: WH
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Taipei Medical University Hospital, Taipei, Taiwan; School of medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Wen-Cheng
authors.initials: WC
authors.lastname: Lo
authors.affiliation: Stem Cell Research Center, Taipei Medical University, Taipei, Taiwan; Graduate Institute of Biomedical Materials and Engineering, College of Oral, Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Wei-Che
authors.initials: WC
authors.lastname: Hsu
authors.affiliation: Stem Cell Research Center, Taipei Medical University, Taipei, Taiwan; Graduate Institute of Biomedical Materials and Engineering, College of Oral, Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Hong-Jian
authors.initials: HJ
authors.lastname: Wei
authors.affiliation: Stem Cell Research Center, Taipei Medical University, Taipei, Taiwan; Graduate Institute of Biomedical Materials and Engineering, College of Oral, Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Hen-Yu
authors.initials: HY
authors.lastname: Liu
authors.affiliation: Department of Orthopaedics and Traumatology, Orthopaedic Research Center, Taipei Medical University Hospital, Taipei, Taiwan.
authors.forename: Chian-Her
authors.initials: CH
authors.lastname: Lee
authors.affiliation: Stem Cell Research Center, Taipei Medical University, Taipei, Taiwan; Graduate Institute of Biomedical Materials and Engineering, College of Oral, Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Szu-Yu
authors.initials: SY
authors.lastname: Tina Chen
authors.affiliation: Department of Family Medicine, Taipei Medical University, Wan Fang Hospital, Taipei, Taiwan.
authors.forename: Ying-Hua
authors.initials: YH
authors.lastname: Shieh
authors.affiliation: Wake Forest Institute of Regenerative Medicine, Winston-Salem, NC, USA.
authors.forename: David F
authors.initials: DF
authors.lastname: Williams
authors.affiliation: Stem Cell Research Center, Taipei Medical University, Taipei, Taiwan; Graduate Institute of Biomedical Materials and Engineering, College of Oral, Medicine, Taipei Medical University, Taipei, Taiwan. Electronic address: wpdeng@tmu.edu.tw.
authors.forename: Win-Ping
authors.initials: WP
authors.lastname: Deng
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D006801:Humans; D006820:Hyaluronic Acid / Q000008:administration & dosage / Q000627:therapeutic use*; D007249:Inflammation / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D007270:Injections, Intra-Articular; D051379:Mice; D010003:Osteoarthritis / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D053657:Platelet-Rich Plasma / Q000166:cytology
chemical_list: D000276:Adjuvants, Immunologic; D006820:Hyaluronic Acid
keywords: Anti-inflammation; Hyaluronic acid (HA); Osteoarthritis (OA); Platelet-rich plasma (PRP); Tissue regeneration