CXCR4 is a response gene for parathyroid hormone which affects osteoblast and osteoclast function in vitro.

Aims: To investigate the role of CXCR4 in response to teriparatide (TPTD) treatment in osteoblasts and osteoclasts.

Methods: Primary murine and human osteoblasts and osteoclasts, MC3T3 cell lines, and hMSC-TERT4 cell lines were treated with TPTD and/or AMD3100, a pharmacological inhibitor of CXCR4. Changes in gene expression, osteoblast viability, mobility, mineralization capacity, and alkaline phosphatase activity were investigated. Osteoclastogenesis and cell fusion were also assessed in response to both treatments.

Results: TPTD increased messenger RNA levels of in all stages of both murine and human osteoblast differentiation. Mineralization analysis showed that CXCR4 was involved in bone matrix formation in response to TPTD. Alkaline phosphatase activity was also impaired by CXCR4 inhibition at early stages of osteoblast differentiation, while it was promoted at late stages, suggesting that CXCR4 could produce a delay in osteoblast maturation. Moreover, we also found a direct activation of osteoclastogenesis after TPTD treatment in murine and human osteoclasts. This process seems to involve CXCR4 activity, since AMD3100-induced CXCR4 inhibition led to a reduction in both murine and human osteoclastogenesis. This process, however, could not be prevented by TPTD treatment.

Conclusion: Our results suggest that is a responsive gene to TPTD treatment, involved in the regulation of osteoblast and osteoclast generation and function. Further in vivo studies are required to confirm this role, and to determine whether pharmacological strategies targeting CXCR4 could potentially improve the treatment outcome for osteoporotic patients.