Osteoblast and osteocyte-specific loss of Connexin43 results in delayed bone formation and healing during murine fracture healing.
Connexin43 (Cx43) plays an important role in osteoblastic differentiation in vitro, and bone formation in vivo. Mice with osteoblast/osteocyte-specific loss of Cx43 display decreased gap junctional intercellular communication (GJIC), bone density, and cortical thickness. To determine the role of Cx43 in fracture healing, a closed femur fracture was induced in Osteocalcin-Cre+; Cx43(flox/flox) (Cx43cKO) and Cre-; Cx43(flox/flox) (WT) mice. We tested the hypothesis that loss of Cx43 results in decreased bone formation and impaired healing following fracture. Here, we show that osteoblast and osteocyte-specific deletion of Cx43 results in decreased bone formation, bone remodeling, and mechanical properties during fracture healing. Cx43cKO mice display decreased bone volume, total volume, and fewer TRAP+ osteoclasts. Furthermore, loss of Cx43 in mature osteoblasts and osteocytes results in a significant decrease in torsional rigidity between 21 and 35 days post-fracture, compared to WT mice. These studies identify a novel role for the gap junction protein Cx43 during fracture healing, suggesting that loss of Cx43 can result in both decreased bone formation and bone resorption. Therefore, enhancing Cx43 expression or GJIC may provide a novel means to enhance bone formation during fracture healing.
Division of Musculoskeletal Sciences, College of Medicine, Pennsylvania State University, 500 University Dr., Mail Code H089, Hershey, Pennsylvania 17033, USA.
Alayna E
AE
Loiselle
Emmanuel M
EM
Paul
Gregory S
GS
Lewis
Henry J
HJ
Donahue
D000818:Animals; D002113:Calcification, Physiologic / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D018031:Connexin 43 / Q000235:genetics* / Q000502:physiology; D005264:Femoral Fractures / Q000473:pathology / Q000503:physiopathology*; D017102:Fracture Healing / Q000502:physiology*; D017629:Gap Junctions / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D010006:Osteoblasts / Q000473:pathology* / Q000502:physiology; D010011:Osteocytes / Q000473:pathology* / Q000502:physiology; D010012:Osteogenesis / Q000502:physiology*; D054159:Torsion, Mechanical
D018031:Connexin 43; C543076:GJA1 protein, mouse