Control of bone resorption in mice by Schnurri-3

MN Wein, DC Jones, JH Shim… - Proceedings of the …, 2012 - National Acad Sciences
MN Wein, DC Jones, JH Shim, AO Aliprantis, R Sulyanto, V Lazarevic, SL Poliachik…
Proceedings of the National Academy of Sciences, 2012National Acad Sciences
Mice lacking the large zinc finger protein Schnurri-3 (Shn3) display increased bone mass, in
part, attributable to augmented osteoblastic bone formation. Here, we show that in addition
to regulating bone formation, Shn3 indirectly controls bone resorption by osteoclasts in vivo.
Although Shn3 plays no cell-intrinsic role in osteoclasts, Shn3-deficient animals show
decreased serum markers of bone turnover. Mesenchymal cells lacking Shn3 are defective
in promoting osteoclastogenesis in response to selective stimuli, likely attributable to …
Mice lacking the large zinc finger protein Schnurri-3 (Shn3) display increased bone mass, in part, attributable to augmented osteoblastic bone formation. Here, we show that in addition to regulating bone formation, Shn3 indirectly controls bone resorption by osteoclasts in vivo. Although Shn3 plays no cell-intrinsic role in osteoclasts, Shn3-deficient animals show decreased serum markers of bone turnover. Mesenchymal cells lacking Shn3 are defective in promoting osteoclastogenesis in response to selective stimuli, likely attributable to reduced expression of the key osteoclastogenic factor receptor activator of nuclear factor-κB ligand. The bone phenotype of Shn3-deficient mice becomes more pronounced with age, and mice lacking Shn3 are completely resistant to disuse osteopenia, a process that requires functional osteoclasts. Finally, selective deletion of Shn3 in the mesenchymal lineage recapitulates the high bone mass phenotype of global Shn3 KO mice, including reduced osteoclastic bone catabolism in vivo, indicating that Shn3 expression in mesenchymal cells directly controls osteoblastic bone formation and indirectly regulates osteoclastic bone resorption.
National Acad Sciences