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.

Preexisting Type 1 Diabetes Mellitus Blunts the Development of Posttraumatic Osteoarthritis

“…Our findings corroborate several studies in mice in which loss of chondrocytes and cartilage tissue in the joints of diabetic animals were reported. (14,15,46,47) However, the severity of OA in our study was much less preeminent than in other studies. This difference in OA severity and responses in the T1DM animals may be explained by several factors such as the use of different animal strains, the age of the animal, the duration of the experiment, type of diabetic model used, and the type of histological assessment of OA.…”

Increased symptoms of stiffness after opening-wedge high tibial osteotomy are associated with worse postoperative knee function outcomes and lower patient satisfaction rate

“…Patients with diabetes often have vascular and neurological disorders, which can affect the normal metabolism and repair capacity of the joints, thereby promoting the development of fibrosis. 28 A preoperative WOMAC stiffness score of 44 or less was a significant predictor of increased stiffness symptoms 1 year after HTO (AUC 0.75, p<.001). WOMAC stiffness score can serve as a screening tool to assess the high-risk population for knee joint stiffness.…”

“…Patients with diabetes often have vascular and neurological disorders, which can affect the normal metabolism and repair capacity of the joints, thereby promoting the development of fibrosis. 28…”

Muscle-Derived Stem/Progenitor Cells Ameliorate Acute Kidney Injury in Rats through the Anti-Apoptotic Pathway and Demonstrate Comparable Effects to Bone Marrow Mesenchymal Stem Cells

“…MDSPCs are characterized by multipotency, long-term proliferation, and self-renewal capacities [31,32]. The most important properties of MDSPCs include their resistance to oxidative and inflammatory stress, induction of neovascularization, and stimulation of regeneration of various tissues, such as bone, cartilage, peripheral nerve, and skeletal muscles [33][34][35][36][37][38][39]. MDSPCs have also demonstrated the ability to extend life and health span in accelerated-aging animal models through paracrine/endocrine mechanisms of action [40].…”