Drug Design, Development and Therapy (Sep 2018)
Sintered dicalcium pyrophosphate treatment attenuates estrogen deficiency-associated disc degeneration in ovariectomized rats
Abstract
Chia-Hsien Chen,1–3 Wei-Chuan Chen,4 Chun-Yi Lin,5 Chih-Hwa Chen,1–3 Yang-Hwei Tsuang,1,2 Yi-Jie Kuo2,6 1Department of Orthopedics, Shuang Ho Hospital, Taipei Medical University, New Taipei, Taiwan; 2Department of Orthopedic Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 3School of Biomedical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan; 4Graduate School of Biotechnology and Bioengineering, Yuan Ze University, Taoyuan City, Taiwan; 5Department of Orthopedic Surgery, Taipei Medical University Hospital, Taipei, Taiwan; 6Department of Orthopedic Surgery, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan Background: Estrogen deficiency is associated with musculoskeletal disorders. Sintered dicalcium pyrophosphate (SDCP) is a novel antiosteoporotic agent. In this study, we examined its use for restoration of bone quality and attenuation of disc degeneration in ovariectomy rats.Methods: Sixty female Sprague Dawley rats were randomly divided into 3 groups, namely sham group undergoing sham surgery, ovariectomy (OVX) group receiving an equivalent volume of isotonic sodium chloride solution, and OVX/SDCP group orally administered with 0.25 mg/mL SDCP. Animals were sacrificed at 3 and 6 months post ovariectomy and lumbar vertebrae and intervertebral discs were harvested. Bone mineral density, micro-computed tomography analysis, and biomechanical testing were performed to assess bone quality. Histological analysis with hematoxylin and eosin, Alcian blue, and Masson’s trichrome stain were conducted to determine disc degeneration. Immunohistochemistry and real-time PCR were carried out to measure the expressions of aggrecan, type I collagen, type II collagen, and MMP-1, MMP-3, and MMP-13.Results: SDCP improved bone quality as observed by the results of increased bone mineral density and stiffness in OVX rats. The improvement in disc degeneration induced by estrogen withdrawal was associated with reduced gene expressions of MMPs and increased production of collagen type II.Conclusion: SDCP prevents osteoporosis and ameliorates disc degeneration in OVX rats. It represents a favorable therapeutic agent for osteoporotic and osteoarthritic conditions in clinical practice. Keywords: sintered dicalcium pyrophosphate, ovariectomy, disc degeneration, matrix metalloprotease, inflammation
