Cell therapy of a knee osteoarthritis rat model using precartilaginous stem cells

M.-P. Fan, M. Si, B.-J. Li, G.-H. Hu, Y. Hou, W. Yang, L. Liu, B. Tang, L. Nie

Department of Orthopaedic Surgery, Qilu Hospital of Shandong University, Jinan, China. 16068622@qq.com

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• Pharmacology

OBJECTIVE: To explore the effect and mechanism of precartilaginous stem cells (PSCs) engraftment-inducing tissue repair in a knee osteoarthritis (OA) rat model.

MATERIALS AND METHODS: Knee osteoarthritis (OA) model was constructed in Sprague Dawley (SD) rats by partial removal of the medial meniscus of the right knee. PSCs were engrafted by injecting precartilaginous stem cells (PSCs) into the right knee cavity. At 4 and 8 weeks after model construction, the serum levels of interleukine (IL)-1β, tumor necrosis factor (TNF)-α, and IL-6 were assessed using enzyme-linked immunosorbent assay (ELISA). Hematoxylin-eosin (HE) staining was performed to assess the histopathology of synovial membrane and cartilage. Western blot analysis was used to assess Notch1, Bcl-2 and Bax levels in the articular cartilage.

RESULTS: At 4 and 8 weeks, OA rats demonstrated significantly higher IL-1β, TNF-α, and IL-6 levels than normal rats (p < 0.05), whereas PSCs treatment prominently attenuated IL-1β upregulation (p < 0.05). In OA rats, the number of chondrocytes dramatically decreased over time in OA rats, with disruption of chondrocytes organization and cell layers. PSCs alleviated the deterioration of cartilage, as evidenced by the relatively smooth articular surface, distinct tidemark and clear cell layers. The model and treatment groups demonstrated substantially higher Notch1 expression. The Bcl-2/Bax value in the OA rats was lower than the control group, while PSCs treatment led to increase in Bcl-2/Bax value.

CONCLUSIONS: PSCs treatment downregulated the expression of inflammatory cytokines, alleviating osteoarthritis in the knee of rats. Notch1 signaling pathway plays an important role in this ameliorating effect of PSCs treatment.

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