Paper of the Month - August 2024
selected by the BMAS Scientific Board
PCLAF induces bone marrow adipocyte senescence and contributes to skeletal aging
Lingqi Xie1, Yalun Cheng1, Biao Hu1, Xin Chen 1 , Yuze An 1 , Zhuying Xia 1 , Guangping Cai1 , Changjun Li 1,2,3 and Hui Peng1
1 – Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital of Central South University, Changsha, Hunan 410008, China;
2 – National Clinical Research Centerfor Geriatric Disorders, Xiangya Hospital, Changsha, Hunan 410008, China and
3 – Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha,Hunan 410008, China
Bone Research, volume 12, Article number: 38 (July 4, 2024)
Bone marrow adipocytes (BMAds) affect bone homeostasis, but the
mechanism remains unclear. Here, we showed that exercise inhibited PCNA
clamp-associated factor (PCLAF) secretion from the bone marrow
macrophages to inhibit BMAds senescence and thus alleviated skeletal
aging. The genetic deletion of PCLAF in macrophages inhibited BMAds
senescence and delayed skeletal aging. In contrast, the transplantation
of PCLAF-mediated senescent BMAds into the bone marrow of healthy mice
suppressed bone turnover. Mechanistically, PCLAF bound to the ADGRL2
receptor to inhibit AKT/mTOR signaling that triggered BMAds senescence
and subsequently spread senescence among osteogenic and osteoclastic
cells. Of note, we developed a PCLAF-neutralizing antibody and showed
its therapeutic effects on skeletal health in old mice. Together, these
findings identify PCLAF as an inducer of BMAds senescence and provide a
promising way to treat age-related osteoporosis.
https://doi.org/10.1038/s41413-024-00337-5 | https://rdcu.be/dTdea
