Role of farnesoid X receptor (FXR) in the process of differentiation of bone marrow stromal cells into osteoblasts.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Bone tissue contains bile acids which accumulate from serum and which can be released in large amounts in the bone microenvironment during bone resorption. However, the direct effects of bile acids on bone cells remain largely unexplored. Bile acids have been identified as physiological ligands of the farnesoid X receptor (FXR, NR1H4). In the present study, we have examined the effects of FXR activation/inhibition on the osteoblastic differentiation of human bone marrow stromal cells (BMSC). We first demonstrated the expression of FXR in BMSC and SaOS2 osteoblast-like cells, and observed that FXR activation by chenodeoxycholic acid (CDCA) or by farnesol (FOH) increases the activity of alkaline phosphatase and the calcification of the extracellular matrix. In addition, we observed that FXR agonists are able to stimulate the expression of osteoblast marker genes [bone sialoprotein (BSP), osteocalcin (OC), osteopontin (OPN) and alkaline phosphatase (ALP)] (FXR involvement validated by shRNA-induced gene silencing), as well as the DNA binding activity of the bone transcription factor RUNX2 (EMSA and ChIP assay). Importantly, we observed that nitrogen-containing bisphosphonates (BPs) inhibit the basal osteoblastic differentiation of BMSC, possibly through suppression of endogenous FOH production, independently of their effects on protein prenylation. Likewise, we found that the FXR

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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