Background Knee osteoarthritis (KOA) seriously affects the quality of life of KOA patients. This study aimed to investigate whether miR-107 could regulate KOA through pyroptosis to affect collagen protein secreted by chondrocytes through IL-1β. Methods The proliferation of chondrocytes was detected by CCK-8 assay. RT-qPCR analysis was used to identify miR-107 expression and transfection effects. The expression of Col II, IL-1β, IL-18, and MMP13 in supernatant of chondrocytes or chondrocytes was detected by ELISA assay and western blot analysis. The pyroptosis of chondrocytes was analyzed by TUNEL assay and the expression of pyroptosis-related proteins was analyzed by western blot. Luciferase reporter assay confirmed the relation of miR-107 to caspase-1. Results The proliferation of chondrocytes was decreased after LPS induction and further decreased by treatment of ATP. Single LPS treatment for chondrocytes downregulated the Col II expression while upregulated the expression of IL-1β, IL-18, and MMP-13, which was further changed by ATP treatment. miR-107 expression was decreased in chondrocytes induced by LPS and further decreased in chondrocytes induced by LPS and ATP. In addition, miR-107 overexpression increased the proliferation and decreased the pyroptosis of chondrocytes induced by LPS and ATP. miR-107 overexpression upregulated the Col II expression while down-regulated the expression of IL-1β, IL-18, and MMP-13 in supernatant of chondrocytes or chondrocytes induced by LPS and ATP. miR-107 overexpression down-regulated the expression of caspase-1, c-caspase-1, GSDMD-N, and TLR4 in chondrocytes induced by LPS and ATP. Furthermore, miR-107 directly targeted caspase-1. Conclusions miR-107 can protect against KOA by downregulating caspase-1 to decrease pyroptosis, thereby promoting collagen protein secreted by chondrocytes by down-regulating IL-1β.

Purpose The present study aims to explore the regulatory function of Sema4D on bone metabolism in combination with leptin or melatonin, as well as the underlying mechanism. Methods The osteoporosis model was established in rats using the OVX method. The bilateral tibial specimens of rats were taken for Micro-CT scanning analysis and three-dimensional reconstruction. The pathological state of bone tissues was evaluated by the HE staining assay. The concentration of estradiol in the serum was detected by the ELISA assay. Six groups were divided in the present study: Control, OVX, OVX + NL, OVX + Sema4D, OVX + Sema4D + leptin, and OVX + Sema4D + MT groups. According to the above grouping, the Sema4D or leptin overexpressing vectors were injected into rats through the tail vein. 3D bone structure was detected by high-resolution micro-CT system. Serum bone-derived alkaline phosphatase (BALP) and tartrate-resistant acid phosphatase-5b (TRAP-5b) activities were measured by ELISA. TRAP staining was used to calculate the number of osteoclasts in the metaphysis of the upper tibia. The expressions of bone morphogenetic protein-2 (BMP-2) and leptin in bone tissue were detected by immunohistochemistry. Results Compared to OVX + NL, the level of V/TV, Tb.N, BMD, and BMC in the OVX + Sema4D + leptin and OVX + Sema4D + MT groups was extremely elevated, accompanied by a declined Tb.Sp level. Compared to the OVX group, in the OVX + Sema4D + leptin and OVX + Sema4D + MT groups, the structure of bone trabeculae was relatively complete and tended to be closely arranged. The number of bone trabeculae was greatly increased and the number of TRAP-positive osteoclasts decreased significantly, accompanied by an upregulation of BMP-2 and leptin, and a declined activity of BALP and TRAP-5b. Conclusion The function of Sema4d on the microstructure of trabecular bone, bone formation, and repairment on the trabecular bone damage in osteoporosis rats was improved by leptin or melatonin.

PurposeThis study aims to examine the effects of leptin and melatonin intervention on bone metabolism in ovariectomize (OVX) rodents, as well as their potential mechanisms of action.MethodsPrepare an OVX model of osteoporosis in rodents and validate the model by collecting bilateral tibia samples for Micro-CT scanning and histological analysis. A control group of normal size, the OVX group, the OVX+Sema4D (Semaphorin 4D) group, the OVX+Sema4D+Leptin group, the OVX+Sema4D+ Melatonin(MT) group and the OVX+Sema4D+Leptin+ MT group were the experimental groups. Adenovirus vector construction and tibial medullary injection validation were conducted in accordance with the aforementioned experimental groups. Four groups of rats were injected with the Sema4D overexpression adenovirus vector into the tibial medullary cavity, and two groups were injected with the Leptin overexpression adenovirus vector. The repair of osteoporosis was observed using micro-CT and histological analysis. Immunohistochemical detection of bone morphogenetic protein-2 (BMP-2) expression in bone tissue was employed to ascertain the amount of osteoclasts in the upper tibial metaphysis, utilizing TRAP(tartrate-resistant acid phosphatase) staining.ResultsIncreased levels of BV/TV, Tb.N, BMD, and BMC were seen in the OVX+ Sema4D+Leptin, OVX+ Sema4D+MT, and OVX+ Sema4D+Leptin+ MT groups compared to the OVX group, whereas Tb. Sp levels were lowered. When compared to the Sema4D overexpression group, the trabecular bone structure of the OVX + Sema4D + Leptin, OVX + Sema4D + MT, and OVX + Sema4D + Leptin + MT groups is largely intact, tends to be closer, and the amount of trabecular bone increases. The OVX + Sema4D + Leptin + MT group in particular.The expression of BMP-2 was dramatically upregulated (p<0.05), the number of TRAP-stained osteoclasts was significantly reduced (p<0.05), and BALP(bone-derived alkaline phosphatase) and TRAP-5b(tartrate-resistant acid phosphatase-5b) activities were significantly downregulated (p<0.05).ConclusionIn rats with osteoporosis, leptin and melatonin can be seen to augment the trabecular microstructure of the bone, augment bone growth, diminish trabecular harm, and mend the bone. The combined effect is more powerful.