Anti-inflammatory treatment using alpha melanocyte stimulating hormone (α-MSH) does not alter osteoblasts differentiation and fracture healing.

BACKGROUND: Alpha-melanocyte-stimulating-hormone (α-MSH) has been identified as a new anti-inflammatory treatment compound in rheumatoid arthritis (RA) and other inflammatory diseases. However, its direct effect on bone cell differentiation or on bone regeneration, which is an inflammatory process, too, has not been investigated, yet. Bone tissue is significantly affected in inflammatory joint diseases. Additionally, inflammatory signaling is essential -in bone regeneration during fracture healing. Therefore, we evaluated the impact of α-MSH-treatment on bone forming cells in an inflammatory setting in vitro and as a treatment approach in a murine fracture healing model in vivo. METHODS: The influence of α-MSH treatment and melanocortin-receptor expression patterns was investigated in vitro in the presence of either IL-1β or/and TNF-α as an inflammatory stimulus. Osteoblast cell function was evaluated by analyzing proliferation and mineralisation capacities. Using quantitative real time PCR, we analyzed mRNA expression of receptors. To explore the impact of α-MSH on bone regeneration in vivo, treatment with α-MSH or NaCl (control) was performed in a murine fracture-healing model using a closed femur fracture stabilized with an intramedullary implant (female, n = 6-8 mice per group). RESULTS: α-MSH-treatment did not impair either proliferation nor mineralisation of osteoblastic cells under native or inflammatory conditions (no significant differences found). All four melanocortin receptor-molecules were expressed in murine osteoblastic cells but in very limited amounts and this did not change upon treatment with inflammatory cytokines or α-MSH or both at the same time. Callus formation in fractured femurs of α-MSH-treated mice was slightly delayed at day 14 post fracture with regard to less cartilage formation (NaCl: 19.9%; α-MSH: 13.5%) and soft tissue remodeling (NaCl: 15.2%; α-MSH: 19.5%) but these results were not significantly different and fracture healing overall occurred in a regular way. CONCLUSION: α-MSH has no negative impact on bone or bone-forming cells in native, inflammatory, or regenerative contexts. We can conclude from our results, that treatment of inflammatory diseases using α-MSH does not interfere significantly with bone regeneration in a murine fracture model and therefore treatment with α-MSH could be continued without negative effects on bone formation and bone regeneration in patients. CLINICAL TRIAL NUMBER: Not applicable.