title: Deletion of Cx43 from osteocytes results in defective bone material properties but does not decrease extrinsic strength in cortical bone.
abstract: Deletion of connexin (Cx) 43 from osteoblasts and osteocytes (OCN-Cre;Cx43(fl/-) mice) or from osteocytes only (DMP1-8kb-Cre;Cx43(fl/fl) mice) results in increased cortical, but not cancellous, osteocyte apoptosis and widening of the femoral midshaft without changes in cortical thickness. Despite the consequent larger moment of inertia, stiffness and ultimate load, measures of mechanical strength assessed by three-point bending, are not higher in either model of Cx43 deficiency due to reduced Young's modulus, a measure of the stiffness of the material per unit of area. In OCN-Cre;Cx43(fl/-) mice, this was accompanied by a reduced ratio of nonreducible/reducible collagen cross-links as assessed by Fourier transformed infrared imaging (FTIRI) in the femoral diaphysis. On the other hand, DMP1-8kb-Cre;Cx43(fl/fl) mice did not show a significant reduction in collagen maturation in the same skeletal site, but a small decrease in mineralization was detected by FTIRI. Remarkably, both osteoblastic and osteocytic cells lacking Cx43 expressed lower mRNA levels of lysyl oxidase, a crucial enzyme involved in collagen maturation. These findings suggest that Cx43 expression in osteoblasts is involved in maintaining the quality of the bone matrix in cortical bone through the maturation of collagen cross-links. Osteocytic Cx43 expression is important also to maintain the stiffness of the bone material, where Cx43 deficiency results in local reduction in mineralization, possibly due to osteocyte apoptosis.
authors.affiliation: Department of Anatomy & Cell Biology, Indiana University School of Medicine, 635 Barnhill Drive, MS-5035, Indianapolis, IN 46202-5120, USA.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Bivi
authors.forename: Mark T
authors.initials: MT
authors.lastname: Nelson
authors.forename: Meghan E
authors.initials: ME
authors.lastname: Faillace
authors.forename: Jiliang
authors.initials: J
authors.lastname: Li
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Miller
authors.forename: Lilian I
authors.initials: LI
authors.lastname: Plotkin
mesh_terms: D000818:Animals; D017209:Apoptosis; D001842:Bone and Bones / Q000737:chemistry* / Q000378:metabolism; D018031:Connexin 43 / Q000235:genetics* / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010011:Osteocytes / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D018031:Connexin 43; C513308:Dmp1 protein, mouse; D016326:Extracellular Matrix Proteins; D012333:RNA, Messenger