Institution: | 1. Department of Orthopedics, Guizhou Provincial People’s Hospital, Guiyang, China
Contribution: Data curation (equal), Investigation (equal), Writing - review & editing (equal);2. Department of Joint, Tianjin Hospital, Tianjin, China
Contribution: Formal analysis (equal), Methodology (equal);3. Department of Orthopedics, Guizhou Provincial People’s Hospital, Guiyang, China
Contribution: Resources (equal), Software (equal);4. Department of Joint, Tianjin Hospital, Tianjin, China
Contribution: Conceptualization (equal), Project administration (equal);5. Department of Joint, Tianjin Hospital, Tianjin, China
Contribution: Writing - original draft (equal);6. Department of Orthopedics, Guizhou Provincial People’s Hospital, Guiyang, China
Contribution: Visualization (equal);7. Department of Orthopedics, Guizhou Provincial People’s Hospital, Guiyang, China
Contribution: Supervision (equal), Validation (equal);8. Department of Joint, Tianjin Hospital, Tianjin, China;9. Department of Orthopedics, Guizhou Provincial People’s Hospital, Guiyang, China |
Abstract: | Glucocorticoid-induced osteonecrosis of the femoral head (GIONFH) is a common orthopaedic disease. GIONFH primarily manifests clinically as hip pain in the early stages, followed by the collapse of the femoral head, narrowing of the hip joint space and damage to the acetabulum, resulting in severely impaired mobility. However, the pathogenesis of GIONFH is not clearly understood. Recently, biomechanical forces and non-coding RNAs have been suggested to play important roles in the pathogenesis of GIONFH. This study aimed to evaluate the role of biomechanical forced and non-coding RNAs in GIONFH. We utilized an in vivo, rat model of GIONFH and used MRI, μCT, GIONFH-TST (tail suspension test), GIONFH-treadmill, haematoxylin and eosin staining, qRT-PCR and Western blot analysis to analyse the roles of biomechanical forces and non-coding RNAs in GIONFH. We used RAW264.7 cells and MC3T3E1 cells to verify the role of MALAT1/miR-329-5p/PRIP signalling using a dual luciferase reporter assay, qRT-PCR and Western blot analysis. The results demonstrated that MALAT1 and PRIP were up-regulated in the femoral head tissues of GIONFH rats, RAW264.7 cells, and MC3T3E1 cells exposed to dexamethasone (Dex). Knockdown of MALAT1 decreased PRIP expression in rats and cultured cells and rescued glucocorticoid-induced osteonecrosis of femoral head in rats. The dual luciferase reporter gene assay revealed a targeting relationship for MALAT1/miR-329-5p and miR-329-5p/PRIP in MC3T3E1 and RAW264.7 cells. In conclusion, MALAT1 played a vital role in the pathogenesis of GIONFH by binding to (‘sponging’) miR-329-5p to up-regulate PRIP. Also, biomechanical forces aggravated the pathogenesis of GIONFH through MALAT1/miR-329-5p/PRIP signalling. |