title: Transplantation of human skeletal muscle-derived progenitor cells ameliorates knee osteoarthritis in streptozotocin-induced diabetic mice.
abstract: The epidemiological and experimental evidence suggests that diabetes can be an independent risk factor for osteoarthritis. The osteoarthritis-like cartilage damage has been shown in streptozotocin-induced diabetic mice. The therapeutic effects of human skeletal muscle-derived progenitor cells (HSMPCs) on diabetic osteoarthritis still remain unclear. Here, we investigated the therapeutic potential of HSMPCs on diabetic knee osteoarthritis. The in vitro chondrogenic ability of HSMPCs was determined by pellet culture assay. Male mice were used to develop the model of streptozotocin-induced type 1 diabetes and its related osteoarthritis. HSMPCs were injected intra-articularly to rescue osteoarthritis. Protein expressions of advanced glycation end-products, cyclooxygenase-2, and type-2 collagen in tissues were determined by immunohistochemistry. The pellet culture assay showed that HSMPCs cultured in differentiation medium for chondrogenesis significantly produced larger pellets with an overproduction of extracellular matrix than in growth medium. In in vivo experiments, intra-articular injection of HSMPCs for 4 weeks significantly prevented the progression of degenerative changes in the cartilage of streptozotocin-induced diabetic mice, including an obvious increase of total articular cartilage thickness and a decrease of fibrous cartilage thickness. HSMPCs transplantation also exerted the decline in advanced glycation end-products and cyclooxygenase-2 protein expression, but increased the type-2 collagen protein expression in streptozotocin-induced osteoarthritic cartilages. Moreover, HSMPCs transplantation also inhibited the increased serum interleukin-6 and matrix metalloproteinase-3 levels in diabetic mice. These results demonstrated for the first time that HSMPCs transplantation ameliorates cartilage degeneration in diabetes-related osteoarthritis mice. These findings suggest that HSMPCs transplantation may apply as a potential therapeutic use of diabetes-related osteoarthritis. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1886-1893, 2017.
authors.affiliation: Department of Geriatrics and Gerontology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Ding-Cheng
authors.initials: DC
authors.lastname: Chan
authors.affiliation: Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan.|Department of Cell and Tissue Engineering, Changhua Christian Hospital, Changhua, Taiwan.
authors.forename: Chen-Yuan
authors.initials: CY
authors.lastname: Chiu
authors.affiliation: Department of Emergency Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Kuo-Cheng
authors.initials: KC
authors.lastname: Lan
authors.affiliation: Department of Forensic Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Te-I
authors.initials: TI
authors.lastname: Weng
authors.affiliation: Departments of Orthopaedics, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Rong-Sen
authors.initials: RS
authors.lastname: Yang
authors.affiliation: Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan.|Department of Pediatrics, College of Medicine, National Taiwan University, Taipei, Taiwan.|Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan.
authors.forename: Shing-Hwa
authors.initials: SH
authors.lastname: Liu
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000209:etiology / Q000601:surgery*; D020219:Chondrogenesis; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D003922:Diabetes Mellitus, Type 1 / Q000150:complications; D006801:Humans; D008297:Male; D008813:Mice, Inbred ICR; D018482:Muscle, Skeletal / Q000166:cytology*; D020370:Osteoarthritis, Knee / Q000209:etiology / Q000601:surgery*; D033581:Stem Cell Transplantation; D014183:Transplantation, Heterologous
keywords: diabetes; human skeletal muscle-derived progenitor cells; osteoarthritis