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

Autor: Pacheco-Costa R; Departamento de Morfologia e Genética, Universidade Federal de Sao Paulo - Escola Paulista de Medicina, São Paulo, Brazil; Department of Anatomy & Cell Biology, Indiana University School of Medicine, Indianapolis, IN, USA. Electronic address: rafa.pacheco@ig.com.br., Kadakia JR; Department of Biomedical Engineering, Indiana University-Purdue University at Indianapolis, IN, USA. Electronic address: jkadakia@umail.iu.edu., Atkinson EG; Department of Anatomy & Cell Biology, Indiana University School of Medicine, Indianapolis, IN, USA. Electronic address: emiatkin@iupui.edu., Wallace JM; Department of Biomedical Engineering, Indiana University-Purdue University at Indianapolis, IN, USA; Department of Orthopaedic Surgery, Indiana University School of Medicine, IN, USA. Electronic address: jmwalla@iupui.edu., Plotkin LI; Department of Anatomy & Cell Biology, Indiana University School of Medicine, Indianapolis, IN, USA; Roudebush Veterans Administration Medical Center, Indianapolis, IN, USA. Electronic address: lplotkin@iupui.edu., Reginato RD; Departamento de Morfologia e Genética, Universidade Federal de Sao Paulo - Escola Paulista de Medicina, São Paulo, Brazil. Electronic address: rejanedr.morf@epm.br.
Jazyk: angličtina
Zdroj: Bone [Bone] 2017 Apr; Vol. 97, pp. 105-113. Date of Electronic Publication: 2017 Jan 16.
DOI: 10.1016/j.bone.2017.01.010
Abstrakt: 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.
(Copyright © 2017 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: