Gnetofuran A Enhances Osteoblast Differentiation through the p38 Signaling Pathway

Gnetofuran A, a newly extracted compound from <i>Gnetum latifolium</i>, possesses anti-inflammatory effects by inhibiting TNF-α activity. However, the function and mechanism of Gnetofuran A in osteoblast differentiation remain unknown. In this study, we found that Gnetofuran A enhanced osteoblast differentiation and upregulated the mRNA levels of osteogenic genes, including <i>alkaline phosphatase</i> (<i>ALP</i>) and <i>osteocalcin</i> (<i>OC</i>). Meanwhile, Gnetofuran A improved protein levels of Runt-related gene 2 (Runx2) and Osterix, the key transcription factors in osteoblast differentiation. Furthermore, we discovered that p38 MAPK signaling is involved in Gnetofuran A-induced osteoblast differentiation. A docking analysis showed the potential interaction between Gnetofuran A and p38. Taken together, our study provides a new biological function of Gnetofuran A and a therapeutic candidate for osteoporosis.