Connexin37 deficiency alters organic bone matrix, cortical bone geometry, and increases Wnt/β-catenin signaling

Rafael Pacheco-Costa, Jay R. Kadakia, Emily G. Atkinson, Joseph M. Wallace, Lilian I. Plotkin, Rejane D. Reginato

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Deletion of connexin (Cx) 37 in mice leads to increased cancellous bone mass due to defective osteoclast differentiation. Paradoxically; however, Cx37-deficient mice exhibit reduced cortical thickness accompanied by higher bone strength, suggesting a contribution of Cx37 to bone matrix composition. Thus, we investigated whether global deletion of Cx37 alters the composition of organic bone extracellular matrix. Five-month-old Cx37−/− mice exhibited increased marrow cavity area, and periosteal and endocortical bone surface resulting in higher total area in tibia compared to Cx37+/+ control mice. Deletion of Cx37 increased genes involved in collagen maturation (loxl3 and loxl4) and glycosaminoglycans- (chsy1, chpf and has3) proteoglycans- associated genes (biglycan and decorin). In addition, expression of type II collagen assessed by immunostaining was increased by 82% whereas collagen maturity by picrosirius-polarizarion tended to be reduced (p = 0.071). Expression of glycosaminoglycans by histochemistry was decreased, whereas immunostaining revealed that biglycan was unchanged and decorin was slightly increased in Cx37−/− bone sections. Consistent with these in vivo findings, MLO-Y4 osteocytic cells silenced for Cx37 gene exhibited increased mRNA levels for collagen synthesis (col1a1 and col3a1) and collagen maturation (lox, loxl1 and loxl2 genes). Furthermore, mechanistic studies showed Wnt/β-catenin activation in MLO-Y4 osteocytic cells, L5 vertebra, and authentic calvaria-derived osteocytes isolated by fluorescent-activated cell sorter. Our findings demonstrate that altered profile of the bone matrix components in Cx37-deficient mice acts in favor of higher resistance to fracture in long bones.

Original languageEnglish (US)
Pages (from-to)105-113
Number of pages9
JournalBone
Volume97
DOIs
StatePublished - Apr 1 2017

Keywords

  • Bone
  • Collagen
  • Connexin 37
  • Glycosaminoglycans
  • Osteocytes
  • Wnt/β-catenin signaling

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Histology

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