Raloxifene inhibits the overexpression of TGF-β1 in cartilage and regulates the metabolism of subchondral bone in rats with osteoporotic osteoarthritis

Abstract

Overexpression of transforming growth factor-beta 1 (TGF-β1) and subchondral bone remodelling play key roles in osteoarthritis (OA). Raloxifene (RAL) reduces the serum level of TGF-β1 in postmenopausal women. However, the effect of RAL on TGF-β1 expression in articular cartilage is still unclear. Therefore, we aimed to investigate the protective effect of RAL on osteoporotic osteoarthritis via affecting TGF-β1 expression in cartilage and the metabolism of subchondral bone. Osteoporotic osteoarthritis was induced by a combination of anterior cruciate transection (ACLT) and ovariectomy (OVX). Rats were divided into five groups (n = 12): The sham group, the ACLT group, the OVX group, the ACLT + OVX group, and the RAL group (ACLT + OVX + RAL, 6.25 mg/kg/day for 12 weeks). Assessment was performed by histomorphology, microcomputed tomography (micro-CT) scan, immunohistochemistry, and tartrate-resistant acid phosphatase (TRAP) staining. We found that severe cartilage degeneration was shown in the ACLT + OVX group. The histomorphological scores, the levels of TGF-β1, and its related catabolic enzymes and osteoclasts numbers in the ACLT + OVX group were higher than those in other groups (p < 0.05). Furthermore, structure model index (SMI) and trabecular spacing (Tb.Sp) were decreased (p < 0.05), while bone mineral density (BMD), bone volume fraction (BV/TV), and trabecular number (Tb.N) were increased by RAL compared with the ACLT + OVX group (p < 0.05). Our findings demonstrated that RAL in clinical doses retards the development of osteoporotic osteoarthritis by inhibiting the overexpression of TGF-β1 in cartilage and regulating the metabolism of subchondral bone. These results provide support for RAL in the expansion of clinical indication for prevention and treatment in postmenopausal osteoarthritis.

The effect of postmenopausal osteoporosis on subchondral bone pathology in a rat model of knee osteoarthritis

“…In our study, coexisting postmenopausal OP in OA rats accelerated the progression of OA pathology. Previous reports also showed that subchondral bone loss induced by OVX accelerated the progression of OA pathology in rodents 21 , 29 , 36 , 37 and rabbits 19 . However, rats with postmenopausal OP alone only echibited a reduction in safranin O staining in the superficial layer of articular cartilage.…”

Using Targeted Metabolomics to Unravel Phenolic Metabolites of Plant Origin in Animal Milk

“…Equol exhibits the highest estrogenic activity among all isoflavones and their metabolites [25]. Recent studies have shown that equol enhances osteoblastic bone formation, prevents bone loss, and protects cartilage and subchondral bone, demonstrating its bone-health properties [26,27]. Additionally, inverse relationships between equol production and various vascular pathologies, including cognitive impairment and dementia, have been observed [28].…”

Intra-Articular Injection of High-Dose ELHLD Peptide for Managing Canine Stifle Osteoarthritis: Kinetic Gait Analysis

“…Previous studies have suggested that inhibition of TGF-β1 may have chondroprotective and regenerative effects in OA of human and rodents (24,26,35). Considering this potential efficacy, intra-articular injection materials that inhibit TGF-β1 have been used in canine OA, but the clinical evidence is still insufficient.…”