title: Intra-articular delivery of sinomenium encapsulated by chitosan microspheres and photo-crosslinked GelMA hydrogel ameliorates osteoarthritis by effectively regulating autophagy.
abstract: Reduced expression of autophagy regulators has been observed in pathological cartilage in humans and mice. The present study aimed to investigate the synergistic therapeutic effect of promotion of chondrocyte autophagy via exposure to sinomenium (SIN) encapsulated by chitosan microspheres (CM-SIN) and photo-crosslinked gelatin methacrylate (GelMA) hydrogel, with the goal of evaluating CM-SIN as a treatment for patients with osteoarthritis. First, we fabricated and characterized GelMA hydrogels and chitosan microspheres. Next, we measured the effect of SIN on cartilage matrix degradation induced by IL1-β in chondrocytes and an ex vivo model. SIN ameliorated the pathological changes induced by IL1-β at least partially through activation of autophagy. Moreover, we surgically induced osteoarthritis in mice, which were injected intra-articularly with CM-SIN and GelMA. Cartilage matrix degradation and chondrocyte autophagy were evaluated 4 and 8 weeks after surgery. Treatment with the combination of CM-SIN and GelMA retarded the progression of surgically induced OA. SIN ameliorated cartilage matrix degradation at least partially by inducing autophagy in vivo. Our results demonstrate that injection of the combination of GelMA hydrogel and CM-SIN could be a promising strategy for treating patients with osteoarthritis.
authors.affiliation: Department of Orthopaedics, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Chen
authors.affiliation: Department of Orthopaedics, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Xia
authors.affiliation: Department of Orthopaedics, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Mei
authors.affiliation: Department of Orthopaedics, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, China.
authors.forename: Jiying
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Orthopaedics, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Shan
authors.affiliation: Department of Orthopaedics, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, China.
authors.forename: Xianfeng
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of Orthopaedics, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, China. Electronic address: shunwu_fan@163.com.
authors.forename: Shunwu
authors.initials: S
authors.lastname: Fan
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D002356:Cartilage / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D048271:Chitosan / Q000138:chemical synthesis / Q000737:chemistry*; D019902:Chondrocytes / Q000187:drug effects / Q000473:pathology; D003432:Cross-Linking Reagents / Q000737:chemistry; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005780:Gelatin / Q000138:chemical synthesis / Q000737:chemistry*; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000138:chemical synthesis / Q000737:chemistry*; D007270:Injections, Intra-Articular; D008027:Light; D008689:Methacrylates / Q000138:chemical synthesis / Q000737:chemistry; D008810:Mice, Inbred C57BL; D008863:Microspheres; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D010003:Osteoarthritis / Q000188:drug therapy* / Q000473:pathology; D010936:Plant Extracts / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D032841:Sinomenium / Q000737:chemistry; D034421:Sus scrofa
chemical_list: D003432:Cross-Linking Reagents; C477012:MAP1LC3A protein, human; C480860:Map1lc3b protein, mouse; D008689:Methacrylates; D008869:Microtubule-Associated Proteins; D010936:Plant Extracts; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D005780:Gelatin; D048271:Chitosan
keywords: Autophagy; Hydrogel; Osteoarthritis; Sinomenium