Interleukin-17 (IL-17) is closely related to osteoarthritis (OA), but animal studies that employ IL-17 to induce OA are currently lacking. Therefore, this study evaluated the effect of IL-17 in the rabbit knee joint. The right knees served as the control group. The left knees were divided randomly into 4 groups: a Hulth group and 3 IL-17 groups (1-ng, 10-ng, and 50-ng groups). OA was induced in the Hulth group using Hulth's method. The IL-17 groups were injected with 1, 10, or 50 ng of IL-17 as indicated. Specimens were collected at 72 h, 1 week, 3 weeks, 6 weeks, and 12 weeks after surgery or the last injection. Subsequently, the following experiments were conducted: X-ray analysis, histological evaluation, and polymerase chain reaction (PCR) analysis of the mRNA expression levels of cartilage degeneration-related markers. At 12 weeks, like the Hulth group, the 10-ng and 50-ng IL-17 groups displayed typical manifestations of OA. The X-ray results, histological scores, and mRNA expression levels showed statistically significant differences between the control group and the 10-ng and 50-ng IL-17 groups. In sum, injecting 10 ng of IL-17 into the rabbit knee joint can induce OA similar to OA induced by Hulth's method.

MicroRNAs (miRs) are a class of small non-coding RNAs and have key roles in various cancer types. Recently, miR-503 has been reported to act as a tumor suppressor in osteosarcoma. However, the detailed mechanism of the regulatory role of miR-503 in osteosarcoma cell proliferation and invasion has largely remained elusive. The present study found that miR-503 was significantly downregulated in osteosarcoma tissues compared to that in matched adjacent non-tumorous tissues. In addition, the expression of miR-503 in osteosarcoma of T3-T4 stage was significantly lower when compared with that in T1-T2 stage samples. miR-503 was also downregulated in osteosarcoma cell lines (Saos-2, MG63, U2OS and SW1353), when compared with that in the normal osteoblast cell line hFOB. Overexpression of miR-503 significantly inhibited the proliferation and invasion of U2OS cells and decreased the protein levels of insulin-like growth factor 1 receptor (IGF-1R), which was further identified as a novel target of miR-503 by a luciferase reporter assay. Moreover, overexpression of IGF-1R eliminated the suppressive effects of miR-503 on the proliferation and invasion of U2OS cells, suggesting that miR-503 inhibits osteosarcoma cell proliferation and invasion by directly targeting IGF-1R. Furthermore, IGF-1R was significantly upregulated in osteosarcoma tissues compared with that in adjacent non-tumor tissues, as well as in osteosarcoma cell lines compared with that in hFOB cells. In addition, the expression levels of IGF-1R were inversely correlated to the miR-503 levels in osteosarcoma tissues, suggesting that the increased IGF-1R expression may be caused by the reduced expression of miR-503. In conclusion, the present study demonstrated that miR-503 suppresses cell proliferation and invasion in osteosarcoma via targeting IGF-1R and thus highlights the importance of miR-503/IGF-1R signaling in the malignant progression of osteosarcoma.

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