MiRNA-140-5p Modulates Cartilage Mechanical Environment by Preserving Surface Stress Homeostasis

Introduction This study explores the interplay between miRNA-140-5p expression and mechanical stress in cartilage within joint biomechanics. Methods Tibial plateau specimens, CT data, and mechanical parameters were obtained from healthy and OA donors. Twenty-four mice, including 12 miRNA-140-5p knockdown (MUT-group) and 12 wild-type (WT group), underwent anterior-cruciate-ligament-transection (ACLT) or sham-operation (SHAM). Finite element analysis, 3D simulation, CT scans, immunohistochemical staining, and fluorescence in situ hybridization were conducted. Primary chondrocytes with or without miRNA-140-5p agomir were loaded mechanically and analyzed by RT-qPCR, Western blot, and phalloidin staining. Results The mechanical coupling unit comprised articular cartilage and subchondral bone, with cartilage apparent compressive modulus linked to the trabecular bone structure ( P < 0.05). Healthy-joint samples and low-stress regions in animal samples exhibited high miRNA-140-5p expression ( P < 0.05) and low RhoA expression. OA or high-stress regions showed the opposite trend ( P < 0.05). MiRNA-140-5p knockdown increased joint loading in mice. In vitro , miRNA-140-5p overexpression reduced RhoA and cytoskeletal remodeling, maintaining chondrocyte mechano-responsiveness. Conclusions Our study reveals a link between mechanical stress and miRNA-140-5p, implying its role in maintaining joint mechanical homeostasis. These findings enhance understanding of biomechanical–molecular interplay, though further studies are needed to assess therapeutic potential in osteoarthritis.