Osteocyte RANKL is required for cortical bone loss with age and is induced by senescence

• DOI: 10.1172/jci.insight.138815
• Publication Date: 2020-09-01T18:30:45Z
• Authors: Ha-Neui Kim; Jinhu Xiong; Ryan S. MacLeod; Srividhya Iyer; Yuko Fujiwara; Keisha M. Cawley; Li Han; Yonghan He; Jeff D. Thostenson; Elisabeth Ferreira; Robert L. Jilka; Daohong Zhou; Maria Almeida; Charles A. O’Brien
• Keywords: Osteocyte; Bone cell; Bone remodeling; Senescence

In aging mice, osteoclast number increases in cortical bone but declines trabecular bone, suggesting that different mechanisms underlie age-associated loss these 2 compartments. Osteocytes produce the osteoclastogenic cytokine RANKL, encoded by Tnfsf11. Tnfsf11 mRNA of aged a mechanism underlying loss. To address this possibility, we mice lacking RANKL osteocytes. Whereas control lost between 8 and 24 months age, osteocytes gained during period. Mice both genotypes with age. Osteoclasts increased age not conditional knockout mice. Induction cellular senescence production murine human cell culture models, an explanation for elevated levels Overexpression senescence-associated transcription factor Gata4 stimulated expression cultured osteoblastic cells. Finally, elimination senescent cells from using senolytic compounds reduced bone. Our results demonstrate requirement osteocyte-derived suggest accumulation