The effects of histamine H1 type receptor (H1R) in regulating osteoblastic cell differentiation and mineralization

Osteoblastic bone formation is important for maintaining the balance of bone turnover. However, the underlying mechanisms are still needed to be elucidated. Histamine H1 type receptor (H1R) is a major subtype of histamine membrane receptors family, which has displayed diverse biological functions in various tissues and cells. In the current study, we have identified a novel physiological function of H1R in regulating osteoblastic differentiation and mineralization of the MC3T3-E1 cells. We found that H1R is expressed in the MC3T3-E1 cells. Interestingly, H1R is up-regulated in the process of differentiation and mineralization of the MC3T3-E1cells induced by osteogenic medium (OM). Blockage of H1R using its specific antagonist Loratadine prevented differentiation and mineralization of the MC3T3-E1 cells by reducing ALP activity, bone matrix deposition, and the expressions of osteogenic marker genes including ALP, OCN, Osx, and type I collagen as well as the transcriptional factor RUNX-2, which is a central regulator of osteoblastogenesis. In contrast, we found that activation of H1R with Histamine exerts opposite actions by increasing the expressions of RUNX-2. Finally, we found that the effects of H1R in osteoblastic differentiation and mineralization are mediated by the AMPK/eNOS signaling. Based on these findings, we concluded that H1R might be an important therapeutic target for the treatment of skeletal disorders.