Connexin 43 hemichannels protect bone loss during estrogen deficiency

Liang Ma, Rui Hua, Yi Tian, Hongyun Cheng, Roberto Jose Fajardo, Joseph J. Pearson, Teja Guda, Daniel Brian Shropshire, Sumin Gu, Jean X. Jiang

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Estrogen deficiency in postmenopausal women is a major cause of bone loss, resulting in osteopenia, osteoporosis, and a high risk for bone fracture. Connexin 43 (Cx43) hemichannels (HCs) in osteocytes play an important role in osteocyte viability, bone formation, and remodeling. We showed here that estrogen deficiency reduced Cx43 expression and HC function. To determine if functional HCs protect osteocytes and bone loss during estrogen deficiency, we adopted an ovariectomy model in wild-type (WT) and two transgenic Cx43 mice: R76W (dominant-negative mutant inhibiting only gap junction channels) and Cx43 Δ130–136 (dominant-negative mutant compromising both gap junction channels and HCs). The bone mineral density (BMD), bone structure, and histomorphometric changes of cortical and trabecular bones after ovariectomy were investigated. Our results showed that the Δ130–136 transgenic cohort had greatly decreased vertebral trabecular bone mass compared to WT and R76W mice, associated with a significant increase in the number of apoptotic osteocyte and empty lacunae. Moreover, osteoclast surfaces in trabecular and cortical bones were increased after ovariectomy in the R76W and WT mice, respectively, but not in ∆130–136 mice. These data demonstrate that impairment of Cx43 HCs in osteocytes accelerates vertebral trabecular bone loss and increase in osteocyte apoptosis, and further suggest that Cx43 HCs in osteocytes protect trabecular bone against catabolic effects due to estrogen deficiency.

Original languageEnglish (US)
Article number11
JournalBone Research
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2019

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Histology

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  • Cite this

    Ma, L., Hua, R., Tian, Y., Cheng, H., Fajardo, R. J., Pearson, J. J., Guda, T., Shropshire, D. B., Gu, S., & Jiang, J. X. (2019). Connexin 43 hemichannels protect bone loss during estrogen deficiency. Bone Research, 7(1), [11]. https://doi.org/10.1038/s41413-019-0050-2