| First Author | Kang KS | Year | 2016 |
| Journal | Bone | Volume | 88 |
| Pages | 138-145 | PubMed ID | 27143110 |
| Mgi Jnum | J:235518 | Mgi Id | MGI:5796708 |
| Doi | 10.1016/j.bone.2016.04.028 | Citation | Kang KS, et al. (2016) Postnatal beta-catenin deletion from Dmp1-expressing osteocytes/osteoblasts reduces structural adaptation to loading, but not periosteal load-induced bone formation. Bone 88:138-45 |
| abstractText | Mechanical signal transduction in bone tissue begins with load-induced activation of several cellular pathways in the osteocyte population. A key pathway that participates in mechanotransduction is Wnt/Lrp5 signaling. A putative downstream mediator of activated Lrp5 is the nucleocytoplasmic shuttling protein beta-catenin (betacat), which migrates to the nucleus where it functions as a transcriptional co-activator. We investigated whether osteocytic betacat participates in Wnt/Lrp5-mediated mechanotransduction by conducting ulnar loading experiments in mice with or without chemically induced betacat deletion in osteocytes. Mice harboring betacat floxed loss-of-function alleles (betacat(f/f)) were bred to the inducible osteocyte Cre transgenic (10)(kb)Dmp1-CreERt2. Adult male mice were induced to recombine the betacat alleles using tamoxifen, and intermittent ulnar loading sessions were applied over the following week. Although adult-onset deletion of betacat from Dmp1-expressing cells reduced skeletal mass, the bone tissue was responsive to mechanical stimulation as indicated by increased relative periosteal bone formation rates in recombined mice. However, load-induced improvements in cross sectional geometric properties were compromised in recombined mice. The collective results indicate that the osteoanabolic response to loading can occur on the periosteal surface when beta-cat levels are significantly reduced in Dmp1-expressing cells, suggesting that either (i) only low levels of beta-cat are required for mechanically induced bone formation on the periosteal surface, or (ii) other additional downstream mediators of Lrp5 might participate in transducing load-induced Wnt signaling. |
