Sp7 Transgenic Mice with a Markedly Impaired Lacunocanalicular Network Induced Sost and Reduced Bone Mass by Unloading

The relationship of lacunocanalicular network structure and mechanoresponse has not been well studied. The lacunocanalicular structures differed in the compression and tension sides, in the regions, and in genders in wild-type femoral cortical bone. The overexpression of Sp7 in osteoblasts resulted in thin and porous cortical bone with increased osteoclasts and apoptotic osteocytes, and the number of canaliculi was half of that in the wild-type mice, leading to a markedly impaired lacunocanalicular network. To investigate the response to unloading, we performed tail suspension. Unloading reduced trabecular and cortical bone in the Sp7 transgenic mice due to reduced bone formation. Sost-positive osteocytes increased by unloading on the compression side, but not on the tension side of cortical bone in the wild-type femurs. However, these differential responses were lost in the Sp7 transgenic femurs. Serum Sost increased in the Sp7 transgenic mice, but not in the wild-type mice. Unloading reduced the Col1a1 and Bglap/Bglap2 expression in the Sp7 transgenic mice but not the wild-type mice. Thus, Sp7 transgenic mice with the impaired lacunocanalicular network induced Sost expression by unloading but lost the differential regulation in the compression and tension sides, and the mice failed to restore bone formation during unloading, implicating the relationship of lacunocanalicular network structure and the regulation of bone formation in mechanoresponse.

Automated summary

The relationship between lacunocanalicular network structure and mechanoresponse has not been well researched. In wild-type femoral cortical bone, there were variations in the lacunocanalicular structures between compression and tension sides, regions, and genders. Overexpression of Sp7 in osteoblasts resulted in thin and porous cortical bone with reduced canaliculi and an impaired lacunocanalicular network. Unloading in Sp7 transgenic mice led to decreased trabecular and cortical bone due to reduced bone formation. Sost-positive osteocytes increased on the compression side in wild-type femurs but not on the tension side. However, these differential responses were lost in Sp7 transgenic femurs. Serum Sost increased in Sp7 transgenic mice but not in wild-type mice. Unloading reduced the expression of Col1a1 and Bglap/Bglap2 in Sp7 transgenic mice but not wild-type mice. Therefore, the impaired lacunocanalicular network in Sp7 transgenic mice induced Sost expression in response to unloading but lost the differential regulation in the compression and tension sides, resulting in a failure to restore bone formation, highlighting the importance of the relationship between lacunocanalicular network structure and regulation of bone formation in mechanoresponse.