MicroRNA-1 small nucleic acid drugs attenuate the progression of osteoarthritis by downregulating Indian hedgehog

Abstract Objective To verify whether MicroRNA-1 (miR-1) small nucleic acid drugs can delay the progression of osteoarthritis (OA) by downregulating Indian hedgehog (Ihh). Methods Costal chondrocytes were isolated from male Sprague-Dawley rats aged 2–3 days. Second-generation chondrocytes were transfected with miR-1 mimic and empty vector with lipo3000 for 6 h and then stimulated with 10 ng/mL IL-1β for 24 h. OA-related genes and cartilage matrix genes were quantified using real-time quantitative polymerase chain reaction (RT–qPCR). Two-month-old Sprague-Dawley rats were divided into three groups: sham operation group + 50 µL saline, anterior cruciate ligament transection (ACLT) group + 50 µL agomiR-1 small nucleic acid drug, and control group ACLT + 50 µL agomiR-1. Treatment was started one week after the operation. All animals were euthanized eight weeks after the operation. X-rays and CT scans were used to detect imaging changes in the articular cartilage. Safranin O staining was used to detect morphological changes in articular cartilage. Immunohistochemistry was used to detect changes in Col2, Col10, metalloproteinase-13 (MMP-13), and other indicators. RT-qPCR was used to detect changes in indicators such as miR-1, Col2, Col10, MMP-13, Ihh, Smo, Gli1, Gli2, and Gli3. Results Overexpression of miR-1 in IL-1β-stimulated chondrocytes reduced the levels of Ihh, MMP-13, and Col10 but increased the levels of Col2 and aggrecan. Intra-articular injection of miR-1 small nucleic acid drugs reduced osteophyte formation and prevented histological cartilage damage. RT-qPCR results indicated that the miR-1 small nucleic acid drug increased articular cartilage anabolism. Conclusions miR-1 small nucleic acid drugs can delay the progression of OA by downregulating Ihh.