Abstract
Background
Knee osteoarthritis (KOA) is a progressively degenerative form of arthritis characterized by chondrocyte apoptosis and cartilage degeneration. KOA also involves limb muscle atrophy, especially in the quadriceps muscles. However, there are limited options for the treatment of KOA. miR-29b stimulates apoptosis in the chondrocytes from patients with KOA and muscle atrophy in other models. Therefore, we investigated the therapeutic effect of miR-29b in cartilage autophagy and muscle atrophy.
Methods
Ten rats comprised the control cohort without anterior cruciate ligament transection. The treatment group (KOA induced in the right knee via anterior cruciate ligament transection) was divided into a model untreated group and a miR-29b-antagomir group (miR-29b antagomir injected 1 wk before surgery).
Results
Real-time polymerase chain reaction revealed successful downregulation of miR-29b using antagomir in the joints and muscles. A weight-bearing test showed that miR-29b downregulation affected joint function. Enzyme-linked immunosorbent assays demonstrated that downregulating miR-29b reduced pro-inflammatory cytokine expression. Immunohistochemistry revealed that miR-29b depletion enhanced autophagy by activating LC3 and beclin-1 in the cartilage. Autophagy was stimulated by the activation of MAPK and mTOR signaling. Depletion of miR-29b ameliorated the decrease in the weight of the quadriceps and the quadriceps weight/body weight ratio of the rats. Hematoxylin–eosin and periodic acid–Schiff staining showed that miR-29b downregulation inhibited muscular atrophy. Immunofluorescence showed that miR-29b downregulation affected IGF/PI3K/AKT signaling.
Conclusions
This study demonstrated the therapeutic effect of miR-29b on autophagy in the cartilage and on muscle atrophy in a rat model for KOA, highlighting the potential of miR-29b as a therapeutic target for KOA.
Histology, Glycosaminoglycan Level and Cartilage Stiffness in Monoiodoacetate-Induced Osteoarthritis: Comparative Analysis with Anterior Cruciate Ligament Transection in Rat Model and Human Osteoarthritis
