Table 6.
Animal studies focused on Connexin-43 in osteocytes
| Targeted cells | Genotype | Baseline skeletal phenotype | External stimulation | Ref. | |
|---|---|---|---|---|---|
| Mechanical | Chemical | ||||
| Global | |||||
| Cx43−/− | Animal die shortly after birth; delayed intramembranous and endochondral ossification during embryogenesis; skeletal abnormalities in clavicles, ribs, vertebrae and limbs. | n/a | n/a | 94 | |
| Cx43R76W | n/a | n/a | Increased osteoclast surface after VOX in WT and Cx43R76W mice, but not in Cx43Δ130–136 mice. | 101 | |
| Cx43Δ130–136 | n/a | n/a | Cx43Δ130–136 mice had significant decreased vertebral trabecular bone mass and increased apoptotic osteocytes in VOX model, compared with WT and Cx43R76W mice. | 101 | |
| Osteoblasts and osteocytes | |||||
| Cola1(I) 2.3-Cre; Cx43–/fl | Normal mice at birth; develop reduced bone formation and defective osteoblast functions at six-month; observed osteocyte loss. | Loaded tibia from CKO mice showed significantly lower mineral apposition rate and bone-formation rate; CKO mice needed ∼40% more force to generate the required endocortical strain. | n/a | 96 | |
| OC-Cre; Cx43–/fl | Increased osteocyte apoptosis in the cortical shell of lumbar vertebrae; increased endocortical resorption, and periosteal bone formation; higher marrow cavity and total tissue areas measured at the femoral mid-diaphysis. | Failed to properly respond to mechanical unloading. | n/a | 97 | |
| OC-Cre; Cx43fl/fl | Osteopenia phenotype in cortical bone, but not in trabecular bone. | Significant bone loss in cortical bone, but not cortical bone, were observed in both CKO mice in HLU experiments; mechanical testing revealed a greater loss of bone strength and rigidity for CKO mice after HLU. | n/a | 99 | |
| Osteocytes | |||||
| Dmp1-Cre; Cx43fl/fl | Increased osteocyte apoptosis with higher prevalence of empty lacunae, but not affect bone mass; reduced prevalence of Opg-expression osteocytes in CKO mice, but no changes for Rankl-positive osteocyte ratio between groups; Reduced the sclerostin levels locally. | n/a | n/a | 97 | |
| Dmp1-Cre; Cx43fl/fl | No difference in animal body weight and bone mineral density. | n/a | CKO mice failed to increase maturity of collagen fibers after PTH injection. | 100 | |
Ref. references, n/a not available, OC osteocalcin, CKO conditional knockout, HLU hindlimb unloading