Bone grafts and biomaterials substitutes for bone defect repair: A review.

Dual effect of strontium ranelate: Stimulation of osteoblast differentiation and inhibition of osteoclast formation and resorption in vitro

Understanding of dopant-induced osteogenesis and angiogenesis in calcium phosphate ceramics

https://www.tpbin.com/Uploads/Subjects/19f1e2d5-5649-481b-ae7b-7ebe80e67e2c.pdf

Antibacterial and biological characteristics of silver containing and strontium doped plasma sprayed hydroxyapatite coatings.

Background and purpose:  Strontium ranelate reduces fracture risk in postmenopausal women with osteoporosis. Evidence from non-clinical studies and analyses of bone markers in phase III trials indicate that this is due to an increase in osteoblast formation and a decrease of osteoclastic resorption. The aim of this work was to investigate, in human cells, the mechanisms by which strontium ranelate is able to influence the activities of osteoblasts and osteoclasts.



Experimental approach:  Human primary osteoblasts were used to examine effects of strontium ranelate on replication (thymidine incorporation), differentiation (Runx2 and alkaline phosphatase) and cell survival (cell counts and caspase activity). Osteoprotegerin (OPG) was measured by quantitative reverse transcription PCR (qRT-PCR) and elisa and receptor activator of NFκB ligand (RANKL) by qRT-PCR and Western blot. As strontium ranelate has been proposed as an agonist of the calcium-sensing receptor (CaSR), the involvement of CaSR in the effects of strontium ranelate on OPG and RANKL expression, and cell replication was examined using siRNA.



Key results:  Strontium ranelate increased mRNA and protein levels of OPG and suppressed those of RANKL. Strontium ranelate also stimulated osteoblast replication and differentiation and increased cell survival under stress. Knocking down CaSR suppressed strontium ranelate-induced stimulation of OPG mRNA, reduction of RANKL mRNA, and increase in replication, indicating the involvement of CaSR in these responses.



Conclusions and implications:  Our results demonstrate that osteoblasts play a key role in the mechanism of action of the anti-fracture agent, strontium ranelate by mediating both its anabolic and anti-resorptive actions, at least in part, via activation of CaSR.

https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1476-5381.2009.00305.x

Osteoblasts play key roles in the mechanisms of action of strontium ranelate

In vitro effects of strontium ranelate on the extracellular calcium-sensing receptor.

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In vitro effects of strontium ranelate on the extracellular calcium-sensing receptor.