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

Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):1281-1287. doi: 10.1080/21691401.2019.1596924.

Abstract

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.

Keywords: AMPK; Histamine H1 type receptor; MC3T3-E1 cells; Osteoporosis; RUNX-2.

MeSH terms

  • 3T3 Cells
  • Animals
  • Cell Differentiation*
  • Core Binding Factor Alpha 1 Subunit / metabolism
  • Mice
  • Minerals / metabolism*
  • Nitric Oxide / metabolism
  • Osteoblasts / cytology*
  • Osteoblasts / metabolism*
  • Osteogenesis
  • Receptors, Histamine H1 / metabolism*

Substances

  • Core Binding Factor Alpha 1 Subunit
  • Minerals
  • Receptors, Histamine H1
  • Nitric Oxide