Abstract:
INTRODUCTION:While the anti-resorptive effects of the bisphosphonates (BPs) are well documented, many questions remain about their mechanisms of action, particularly following long-term use. This study evaluated the effects of alendronate (Ale) treatment on TGF-β1 signaling in mesenchymal stem cells (MSCs) and osteocytes, and the relationship between prolonged alendronate treatment on systemic TGF-β1 levels and bone strength. METHODS:TGF-β1 expression and signaling were evaluated in MSCs and osteocytic MLO-Y4 cells following Ale treatment. Serum total TGF-β1 levels, a bone resorption marker (DPD/Cr), three-dimensional microCT scans and biomechanical tests from both the trabecular and cortical bone were measured in ovariectomized rats that either received continuous Ale treatment for 360 days or Ale treatment for 120 days followed by 240 days of vehicle. Linear regression tests were performed to determine the association of serum total TGF-β1 levels and both the trabecular (vertebrae) and cortical (tibiae) bone strength. RESULTS:Ale increased TGF-β1 signaling in the MSCs but not in the MLO-Y4 cells. Ale treatment increased serum TGF-β1 levels and the numbers of TGF-β1-positive osteocytes and periosteal cells in cortical bone. Serum TGF-β1 levels were not associated with vertebral maximum load and strength but was negatively associated with cortical bone maximum load and ultimate strength. CONCLUSIONS:The increase of serum TGF-β1 levels during acute phase of estrogen deficiency is likely due to increased osteoclast-mediated release of matrix-derived latent TGF-β1. Long-term estrogen-deficiency generally results in a decline in serum TGF-β1 levels that are maintained by Ale treatment. Measuring serum total TGF-β1 levels may help to determine cortical bone quality following alendronate treatment.
journal_name
Bonejournal_title
Boneauthors
Jia J,Yao W,Amugongo S,Shahnazari M,Dai W,Lay YA,Olvera D,Zimmermann EA,Ritchie RO,Li CS,Alliston T,Lane NEdoi
10.1016/j.bone.2012.10.017subject
Has Abstractpub_date
2013-01-01 00:00:00pages
424-32issue
1eissn
8756-3282issn
1873-2763pii
S8756-3282(12)01325-7journal_volume
52pub_type
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