circ_0003204 regulates the osteogenic differentiation of human adipose-derived stem cells via miR-370-3p/HDAC4 axis

Human adipose-derived stem cells(hASCs)are a promising cell type for bone tissue regeneration.Circular RNAs(circRNAs)have been shown to play a critical role in regulating various cell differentiation and involve in mesenchymal stem cell osteogenesis.However,how circRNAs regulate hASCs in osteogenesis is still unclear.Herein,we found circ_0003204 was significantly downregulated during osteogenic differentiation of hASCs.Knockdown of circ_0003204 by si RNA or overexpression by lentivirus confirmed circ_0003204 could negatively regulate the osteogenic differentiation of hASCs.We performed dual-luciferase reporting assay and rescue experiments to verify circ_0003204 regulated osteogenic differentiation via sponging miR-370-3p.We predicted and confirmed that miR-370-3p had targets in the 3′-UTR of HDAC4 m RNA.The following rescue experiments indicated that circ_0003204 regulated the osteogenic differentiation of hASCs via miR-370-3p/HDAC4 axis.Subsequent in vivo experiments showed the silencing of circ_0003204 increased the bone formation and promoted the expression of osteogenic-related proteins in a mouse bone defect model,while overexpression of circ_0003204 inhibited bone defect repair.Our findings indicated that circ_0003204 might be a promising target to promote the efficacy of hASCs in repairing bone defects.

Lithium chloride promotes osteogenesis and suppresses apoptosis during orthodontic tooth movement in osteoporotic model via regulating autophagy

Osteoporosis is a widely distributed disease that may cause complications such as accelerated tooth movement,bone resorption,and tooth loss during orthodontic treatment.Promoting bone formation and reducing bone resorption are strategies for controlling these complications.For several decades,the autophagy inducer lithium chloride(LiCl)has been explored for bipolar.In this study,we investigated the autophagy-promoting effect of LiCl on bone remodeling under osteoporotic conditions during tooth movement.Ovariectomy was used to induce osteoporosis status in vivo.The results showed that LiCl rejuvenated autophagy,decreased apoptosis,and promoted bone formation,thus protecting tooth movement in osteoporotic mice.Furthermore,in vitro experiments showed that LiCl reversed the effects of ovariectomy on bone marrow-derived mesenchymal stem cells(BMSCs)extracted from ovariectomized mice,promoting osteogenesis and suppressing apoptosis by positively regulating autophagy.These findings suggest that LiCl can significantly decrease adverse effects of osteoporosis on bone remodeling,and that it has great potential significance in the field of bone formation during tooth movement in osteoporosis patients.