Halofuginone delays articular cartilage degeneration in early osteoarthritis / 中国组织工程研究

ABSTRACT

BACKGROUND: Halofuginone has been proved to ameliorate the pathogenesis of osteoarthritis.OBJECTIVE: To further verify the protective effect of halofuginone on early osteoarthritis.METHODS: Forty-five healthy male C57BL6J mice were randomly divided into three groups (n=15 per group) the mice in sham operation group were only subjected to right knee capsulotomy; in the other two groups, animal models of osteoarthritis were established by cutting off the right anterior cruciate ligament, followed by treated with distilled water (placebo group) or 0.5 mg/kg halofuginone (halofuginone group) via gavage, once daily beginning at 3 days after modeling. Twenty-eight days after treatment, all mice were sacrificed and the right knee was removed. The morphology and structure of the joint tissue were observed by hematoxylin-eosin staining and safranin fast green staining; the expression of transforming growth factor-β1 (TGF-β1) was detected by immunohistochemistry.RESULTS AND CONCLUSION: The structure of articular cartilage in the sham operation group was normal, the cells arranged in neat rows, and the articular surface was not worn. In the placebo group, the articular cartilage layer became thinner, the cartilage surface was worn and even fragmented, and cells arranged in disorder. In the halofuginone group,the cartilage cell layer was clear and tidy, with regular cell morphology. The hyaline cartilage thickness and hyaline cartilage thickness/calcified cartilage thickness were ranked as follows sham operation group > halofuginone group >placebo group. The calcified cartilage thickness was the highest in the placebo group, followed by halofuginone group,and lowest in the sham operation group. Osteoarthritis Research Society International scores and TGF-β1 positive cells/chondrocytes in the halofuginone group were significantly lower than those in the placebo group, and all above indices showed significant differences among groups (P < 0.05). These results suggest that halofuginone via gavage can partially prevent articular cartilage degeneration in early osteoarthritis mice probably by downregulating the expression of TGF-β1, thus delaying the progression of osteoarthritis.