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

  • Shao-Hua Ping Department of Orthopedic Surgery, Hebei Medical University, Shijiazhuang, China https://orcid.org/0000-0002-2560-851X
  • Fa-Ming Tian Medical Research Center, North China University of Science and Technology, Tangshan, China
  • Hao Liu Department of Orthopedic Surgery, Affiliated Hospital of North China University of Science and Technology, Tangshan, China https://orcid.org/0000-0003-0994-1256
  • Qi Sun Department of Orthopedic Surgery, Hebei Medical University, Shijiazhuang, China https://orcid.org/0000-0002-2679-9960
  • Li-Tao Shao Department of Orthopedic Surgery, Hebei Medical University, Shijiazhuang, China https://orcid.org/0000-0003-0962-3266
  • Qiang-Qiang Lian Department of Orthopedic Surgery, the Affiliated Hospital of North China University of Science and Technology, Tangshan, China
  • Liu Zhang Department of Orthopedic Surgery, Hebei Medical University, Shijiazhuang, China; Department of Orthopedic Surgery, Emergency General Hospital, Beijing, China https://orcid.org/0000-0001-5239-3561
Keywords: Osteoporosis, osteoarthritis, raloxifene, TGF-β1, cartilage, subchondral bone

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.

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Raloxifene inhibits the overexpression of TGF-β1 in cartilage and regulates the metabolism of subchondral bone in rats with osteoporotic osteoarthritis
Published
2020-11-19
How to Cite
1.
Ping S-H, Tian F-M, Liu H, Sun Q, Shao L-T, Lian Q-Q, Zhang L. Raloxifene inhibits the overexpression of TGF-β1 in cartilage and regulates the metabolism of subchondral bone in rats with osteoporotic osteoarthritis. Bosn J of Basic Med Sci [Internet]. 2020Nov.19 [cited 2021Mar.6];. Available from: https://www.bjbms.org/ojs/index.php/bjbms/article/view/5142
Section
Pathology

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