TY - JOUR
T1 - Sintered dicalcium pyrophosphate treatment attenuates estrogen deficiency-associated disc degeneration in ovariectomized rats
AU - Chen, Chia Hsien
AU - Chen, Wei Chuan
AU - Lin, Chun Yi
AU - Chen, Chih Hwa
AU - Tsuang, Yang Hwei
AU - Kuo, Yi Jie
N1 - Funding Information:
This study was supported by Grant from Taipei Medical University (TMU104-AE1-B20).
Publisher Copyright:
© 2018 Chen et al.
PY - 2018/1/1
Y1 - 2018/1/1
N2 - 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.
AB - 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.
KW - disc degeneration
KW - inflammation
KW - matrix metalloprotease
KW - ovariectomy
KW - sintered dicalcium pyrophosphate
KW - Ovariectomy
KW - Administration, Oral
KW - Calcium Pyrophosphate/administration & dosage
KW - Rats
KW - Rats, Sprague-Dawley
KW - X-Ray Microtomography
KW - Estrogens/deficiency
KW - Animals
KW - Female
KW - Intervertebral Disc Degeneration/drug therapy
UR - http://www.scopus.com/inward/record.url?scp=85054349584&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85054349584&partnerID=8YFLogxK
U2 - 10.2147/DDDT.S170816
DO - 10.2147/DDDT.S170816
M3 - Article
C2 - 30271118
AN - SCOPUS:85054349584
SN - 1177-8881
VL - 12
SP - 3033
EP - 3041
JO - Drug Design, Development and Therapy
JF - Drug Design, Development and Therapy
ER -