Bone Abstracts

Mechanical stimulation triggers periostin (Postn) expression in the periosteum and osteocytes (Oc), which downregulates Sost and activates β-catenin signaling. Hence the cortical bone response to loading is abolished in Postn^−/− mice. Here we investigated the role of Oc β-catenin and its interaction with Postn on the bone biomechanical response. Postn^−/− were bred with Oc-Ctnn^−/− mice to generate Postn^+/−;Oc-Ctnn^+/+ and Postn^+/+;Oc-Ctnn^+/− heterozygotes, Postn^+/−;Oc-Ctnn^+/− double heterozygotes, Postn^−/−;Oc-Ctnn^+/+ and their WT littermate. In vivo cyclic axial compression (40 cycles, 1500 peak microstrain, 7 min, 3 days/week) was applied to the left tibia for 2 weeks, while the non-loaded tibia served as paired control. Postn^+/+;Oc-Ctnn^−/−, Postn^+/−;Oc-Ctnn^−/− and double KO mice sustained a high rate of spontaneous fractures and death, and were therefore not subjected to mechanical stimulation. Postn^+/−;Oc-Ctnn^+/+ were not different from WT, whereas Postn^+/+;Oc-Ctnn^+/− have significantly lower femoral BMD, BV/TV, CtBV, and CtTh (−8, −28, −6.2, and −5.8%, respectively, P<0.05). Double heterozygous mice were similar to Postn^+/+;Oc-Ctnn^+/−, indicating a predominant influence of Oc β-catenin on bone mass and structure. Following axial compression, tibial BMD gain was similar in Postn^+/+;Oc-Ctnn^+/−, Postn^+/−;Oc-Ctnn^+/+; and WT mice (+11.2±0.6 mg/cm²), indicating that neither Postn nor Ctnn haploinsufficiency impaired the biomechanical response. In contrast, BMD gain was significantly lower in Postn^+/−;Oc-Ctnn^+/− (+7.9±1.0 mg/cm²) and Postn^−/−;Oc-Ctnn^+/+(+4.8±1.2 mg/cm²) (P<0.05 compared to the other groups). Similarly, CtTV and CtBV increased 12% to 17% in the stimulated vs non-stimulated tibia of Postn^+/+;Oc-Ctnn^+/+, Postn^+/−;Oc-Ctnn^+/+ and Postn^+/+;Oc-Ctnn^+/− (all P<0.05), but not in Postn^+/−;Oc-Ctnn^+/− nor in Postn^−/−;Oc-Ctnn^+/+. BV/TV increased with loading independtly of the genotype. In conclusions, β-catenin haploinsufficiency in osteocytes affects post-natal bone remodelling but not the modelling induced by axial compression. However, the concomitant loss of one β-catenin and one periostin allele impairs the cortex biomechanical response, which implies that periostin and β-catenin expression in osteocytes synergize to mediate skeletal adaptation to loading.