Calcitonin suppresses intervertebral disk degeneration and preserves lumbar vertebral bone mineral density and bone strength in ovariectomized rats
We investigated the effect of calcitonin (CT) on lumbar intervertebral disk degeneration (LIDD) in rats with ovariectomy-induced osteopenia. CT protected ovariectomized rats from LIDD by, at least in part, modifying extracellular matrix metabolism of the disks and preserving the microarchitecture and biomechanical properties of adjacent vertebrae.
The present study aimed to investigate the effect of CT on lumbar vertebral bone mineral density and intervertebral disk degeneration in ovariectomized (OVX) rats.
We first subjected 50 3-month-old female rats to either OVX (n = 30) or sham (n = 20). Twelve weeks later, ten OVX and ten sham rats were necropsied. The remaining OVX rats began to receive either saline vehicle (OVX + V, n = 10), or salmon CT (OVX + CT, 16 IU/kg/2 days, n = 10). After 12 weeks of treatment, necropsy was conducted and bone mineral density was determined in L3–4 and L5–6 vertebrae. The microstructure and biomechanical properties of L3 vertebrae were detected by micro-computed tomography and compression test, respectively. L5–6 was also used to measure intervertebral disk height and observe intervertebral disk histological changes by Van Gieson staining and histological scores, as well as immunohistochemistry (IHC) analysis of matrix metalloprotease (MMP)-1, MMP-13, and collagen II expression.
At 12 weeks post-OVX, OVX rats had lower BV/TV and Tb.N and higher intervertebral disk histological score than sham rats. After 24 weeks, OVX + CT rats had higher BMD, BV/TV, Tb.N, and bone biomechanical strength values than OVX + V rats. Histological analysis showed OVX + CT rats had significantly lower disk degeneration scores than OVX + V rats. IHC analysis revealed CT treatment decreased expression of MMP-1 and MMP-13 and increased expression of collagen II compared with OVX + V rats.
Our data demonstrate that CT-treated OVX rats display less intervertebral disk degeneration and favorable changes in intervertebral disk metabolism, associated with higher trabecular bone mass, better trabecular microarchitecture, and better biomechanical strength when compared to vehicle-treated OVX rats.
KeywordsBiomechanics Intervertebral disk degeneration Micro-computed tomography Osteopenia Salmon calcitonin
This work was supported by the National Natural Science Foundation of China (NSFC 31171136), the Natural Science Foundation of Hebei Province (H2013209255 and H2013209257), and the Science and Technology Project of Hebei Province (11276106D).
Conflict of interest
Fa-ming Tian, Kai Yang, Wen-ya Wang, Yang Luo, Shu-yang Li, Hui-ping Song, Ying-ze Zhang, Yong Shen, and Liu Zhang declare that they have no conflict of interest.
- 10.Sondergaard BC, Wulf H, Henriksen K, Schaller S, Oestergaard S, Qvist P, Tankó LB, Bagger YZ, Christiansen C, Karsdal MA (2006) Calcitonin directly attenuates collagen type II degradation by inhibition of matrix metalloproteinase expression and activity in articular chondrocytes. Osteoarthritis Cartilage 14:759–768CrossRefPubMedGoogle Scholar
- 17.Wang YX, Griffith JF, Ma HT, Kwok AW, Leung JC, Yeung DK, Ahuja AT, Leung PC (2011) Relationship between gender, bone mineral density, and disc degeneration in the lumbar spine: a study in elderly subjects using an eight-level MRI-based disc degeneration grading system. Osteoporos Int 22:91–96CrossRefPubMedGoogle Scholar
- 18.Wang YX, Kwok AW, Griffith JF, Leung JC, Ma HT, Ahuja AT, Leung PC (2011) Relationship between hip bone mineral density and lumbar disc degeneration: a study in elderly subjects using an eight-level MRI-based disc degeneration grading system. J Magn Reson Imaging 33:916–920CrossRefPubMedGoogle Scholar
- 22.Zheng SX, Vrindts Y, Lopez M, De Groote D, Zngerle PF, Collette J, Franchimont N, Geenen V, Albert A, Reginster JY (1997) Increase in cytokine production (IL-1b, IL-6, TNF-a but not IFN-g, GM-CSF or LIF) by stimulated whole blood cells in postmenopausal osteoporosis. Maturitas 26:63–71CrossRefPubMedGoogle Scholar
- 26.Gooi JH, Pompolo S, Karsdal MA, Kulkarni NH, Kalajzic I, McAhren SH, Han B, Onyia JE, Ho PW, Gillespie MT, Walsh NC, Chia LY, Quinn JM, Martin TJ, Sims NA (2010) Calcitonin impairs the anabolic effect of PTH in young rats and stimulates expression of sclerostin by osteocytes. Bone 46:1486–1497CrossRefPubMedGoogle Scholar
- 32.Pelletier JP, Kapoor M, Fahmi H, Lajeunesse D, Blesius A, Maillet J, Martel-Pelletier J (2013) Strontium ranelate reduces the progression of experimental dog osteoarthritis by inhibiting the expression of key proteases in cartilage and of IL-1β in the synovium. Ann Rheum Dis 72:250–257CrossRefPubMedGoogle Scholar