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Bone Abstracts (2016) 5 P418 | DOI: 10.1530/boneabs.5.P418

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CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India.


Adiponectin has recently been shown to influence skeletal metabolism. Over-expression of adiponectin gene suppresses bone resorption and increases trabecular bone mass. Bone marrow stromal cells from adiponectin-null mice had reduced mineralized nodule formation ability compared with wild type mice. Adiponectin, signalling via the adiponectin receptor 1 (AdipoR1) stimulates osteoblast differentiation and inhibits osteoclastogenesis. We have shown that the globular form of adiponectin (gAd) signals via AdipoR1 and stimulates osteoblast differentiation. Based on this observation, we hypothesized that gAd could restore bones in osteopenic rats.

Methodology: A prior approval from Institutional Animal Ethics Committee was obtained. Endotoxin free recombinant gAd was prepared in-house. Adult Sprague dawley rats (200±10 g) were either sham-operated (ovary intact) or ovariectomized (OVX) and left untreated for 12 weeks for trabecular osteopenia to develop in the OVX group. Rats were then randomized into following groups (n=8); sham+vehicle (0.9% saline); OVX+vehicle, OVX+gAd (10 μg/rat, i.p.), OVX+gAd (100 μg/rat, i.p.), OVX+hPTH (1–34) (40 μg/kg/day, 5 days/week, i.p.) and OVX+alendronate (3 mg/kg/day, orally). Bone parameters were measured by micro-computed tomography. Data are expressed as mean±S.E.M., data analysed using non parametric ANOVA followed by Dunnett’s multiple comparisons test using GraphPad Prism5.

Results: OVX+vehicle group showed a dramatic loss of trabecular bones at distal femur compared with the sham (control). gAd had a dose-dependent effect in restoring the trabecular bones of OVX rats. At its highest dose (100 μg), gAd restored trabecular bone volume per tissue volume (BV/TV%), trabecular thickness, trabecular number and trabecular spacing to the level of control. The skeletal effect of PTH however, was superior to gAd at its highest dose. (Table 1)

Table 1.
ShamOvx+VehOvx+PTHOvx+ALNOvx+gAd10Ovx+gAd100
BV/TV20.2±1.2***10.6±1.324.4±1.4***16.2±0.6**16.0±1.5**17.4±0.5***
P>0.05*, P≤0.05, **P≤0.01, *** P≤0.001.

Summary: In a preclinical model of post-menopausal osteoporosis, we showed therapeutic efficacy of gAd in restoring trabecular bones.

Volume 5

43rd Annual European Calcified Tissue Society Congress

Rome, Italy
14 May 2016 - 17 May 2016

European Calcified Tissue Society 

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