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Alendronate affects osteoblast functions by crosstalk through EphrinB1-EphB
E Shimizu1, J Tamasi, N C Partridge
1New York University College of Dentistry, Department of Basic Science and Craniofacial Biology, USA. es152@nyu.edu
Journal of Dental Research
|December 20, 2011
Summary
Alendronate, a bisphosphonate, may impair bone healing by altering cell communication. It increases ephrinB1 expression in pre-osteoclasts, which then suppresses osteoblast function via EphB receptors.
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- Bisphosphonates treat osteoporosis but have unclear mechanisms for side effects like delayed healing.
- Osteoporosis treatment involves managing bone remodeling, where osteoblasts build bone and osteoclasts resorb it.
Purpose of the Study:
- To investigate the hypothesis that alendronate inhibits osteoblast function by disrupting osteoclast-osteoblast coupling via ephrinB-EphB signaling.
- To elucidate the molecular mechanisms behind bisphosphonate-induced bone healing complications.
Main Methods:
- Adult mice were treated with alendronate for 8 weeks.
- Gene and protein expression of ephrinB1, EphB1, EphB3, bone sialoprotein (BSP), and osteonectin were analyzed in femurs and bone marrow cells.
- Osteoblast differentiation was assessed after depleting pre-osteoclasts.
Main Results:
- Alendronate increased ephrinB1 and EphB1/B3 expression in mouse femurs.
- Alendronate suppressed bone sialoprotein and osteonectin expression in osteoblasts.
- Alendronate's effects on osteoblast differentiation were dependent on the presence of pre-osteoclasts.
- Alendronate upregulated ephrinB1 in pre-osteoclasts and EphB1/B3 in osteoblasts, with ephrinB1 reverse signaling inhibiting osteoblast differentiation.
Conclusions:
- Alendronate appears to inhibit osteoblast differentiation indirectly by modulating ephrinB1/EphB signaling between pre-osteoclasts and osteoblasts.
- This pathway provides a potential mechanism for bisphosphonate-associated bone healing impairments.
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