biostudies-literatureUnknown16(1)Huang J<b>Background:</b> Osteoporosis is a major public health concern worldwide. As the predominant and long-lived bone cells, osteocytes serve as key regulators of bone remodeling and mechanotransduction. However, the molecular mechanisms underlying their regulatory roles remain poorly understood. The roles of talin1, a key focal adhesion protein linking integrins to the cytoskeleton, in regulation of osteocyte function and skeletal homeostasis remain unclear. <b>Methods:</b> Osteocyte-specific talin1 conditional knockout (cKO) mice were established, and their skeletal phenotypes were assessed through micro-CT, histomorphometry, and biomechanical analyses. Osteocyte senescence and molecular signaling were assessed by RNA sequencing analysis, immunostaining, and biochemical assays. Talin1-p53 iTheranostics465-482https://www.ebi.ac.uk/biostudies/studies/S-EPMC12665141biostudies-literatureThe talin1-p53 axis inhibits osteocyte senescence to promote bone mass and mediate skeletal adaptation to mechanical stimulation.PMC12665141Yang HWu MYang JQin LYan QLin SHuang JChen HYi WGong WZhang PHe SZhang XXiao GWang YfalseThe talin1-p53 axis inhibits osteocyte senescence to promote bone mass and mediate skeletal adaptation to mechanical stimulation.<b>Background:</b> Osteoporosis is a major public health concern worldwide. As the predominant and long-lived bone cells, osteocytes serve as key regulators of bone remodeling and mechanotransduction. However, the molecular mechanisms underlying their regulatory roles remain poorly understood. The roles of talin1, a key focal adhesion protein linking integrins to the cytoskeleton, in regulation of osteocyte function and skeletal homeostasis remain unclear. <b>Methods:</b> Osteocyte-specific talin1 conditional knockout (cKO) mice were established, and their skeletal phenotypes were assessed through micro-CT, histomorphometry, and biomechanical analyses. Osteocyte senescence and molecular signaling were assessed by RNA sequencing analysis, immunostaining, and biochemical assays. Talin1-p53 i2026-01-01T00:00:00Z20262026-07-15T13:25:13.691Z2026-07-05T03:08:30.2ZS-EPMC126651414132835010.7150/thno.123532