LINC00370 modulates miR-222-3p-RGS4 axis to protect against osteoporosis progression

Background: We aimed to determine the role of the LINC00370/miR-222-3p/RGS4 axis in modulating the process of adipose-derived stem cell (ADSC) osteogenic differentiation. Methods: We first evaluated the differential expression of LINC00370, miR-222-3p and RGS4 between normal and osteogenically induced ADSCs. Moreover, we transfected ADSCs with LINC00370 siRNA and an miR-222-3p inhibitor to determine the role of LINC00370 in modulating the process of ADSC osteogenic differentiation. Finally, we analyzed the dual-luciferase reporter gene to identify the relationship between LINC00370 and miR222-3p. We first created osteoporotic rat models by ovariectomy (OVX) and treated with pcDNA-LINC00370. HE and immunohistochemical staining of OCN were performed to assess the changes in bone microarchitecture. Results: LINC00370 and RGS4 expression was remarkably upregulated in the osteogenic ADSC group compared with the normal medium group. On the other hand, miR-222-3p expression was remarkably decreased in the osteogenic group compared with the normal medium group. Knockdown of LINC00370 reduced the osteogenic differentiation of ADSCs. Moreover, the inhibitor of miR-222-3p partially reversed the reduction of osteogenic differentiation by LINC00370 knockdown. Knockdown of LINC00370 reduced the expression of p-Akt and pPI3K. The inhibitor of miR-222-3p partially reversed the reduction of the expression of p-Akt and p-PI3K by LINC00370 knockdown. A dual luciferase reporter assay indicated that LINC00370 can directly bind miR-222-3p. LINC00370 suppressed OP progression in OVX and partially upregulated OCN protein expression. Conclusion: Collectively, the above results confirm that LINC00370 promotes the process of ADSC osteogenic differentiation via the miR-222-3p/RGS4 axis. Moreover, LINC00370 could protect against OVX-induced OP.

Automated summary

The study showed that LINC00370 promotes the osteogenic differentiation of adipose-derived stem cells through the miR-222-3p/RGS4 axis, as well as protects against osteoporosis induced by ovariectomy.