{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T10:08:16Z","timestamp":1791972496645,"version":"4.3.4"},"reference-count":54,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2021,8,28]],"date-time":"2021-08-28T00:00:00Z","timestamp":1630108800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100017950","name":"Shanghai Municipal Health Commission","doi-asserted-by":"publisher","award":["GWV-10.1-XK10"],"award-info":[{"award-number":["GWV-10.1-XK10"]}],"id":[{"id":"10.13039\/100017950","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cellular senescence and its senescence-associated secretory phenotype (SASP) are widely regarded as promising therapeutic targets for aging-related diseases, such as osteoporosis. However, the expression pattern of cellular senescence and multiple SASP secretion remains unclear, thus leaving a large gap in the knowledge for a desirable intervention targeting cellular senescence. Therefore, there is a critical need to understand the molecular mechanism of SASP secretion in the bone microenvironment that can ameliorate aging-related degenerative pathologies including osteoporosis. In this study, osteocyte-like cells (MLO-Y4) were induced to cellular senescence by 2 Gy \u03b3-rays; then, senescence phenotype changes and adverse effects of SASP on bone marrow mesenchymal stem cell (BMSC) differentiation potential were investigated. The results revealed that 2 Gy irradiation could hinder cell viability, shorten cell dendrites, and induce cellular senescence, as evidenced by the higher expression of senescence markers p16 and p21 and the elevated formation of senescence-associated heterochromatin foci (SAHF), which was accompanied by the enhanced secretion of SASP markers such as IL-1\u03b1, IL-6, MMP-3, IGFBP-6, resistin, and adiponectin. When 0.8 \u03bcM JAK1 inhibitors were added to block SASP secretion, the higher expression of SASP was blunted, but the inhibition in osteogenic and adipogenic differentiation potential of BMSCs co-cultured with irradiated MLO-Y4 cell conditioned medium (CM- 2 Gy) was alleviated. These results suggest that senescent osteocytes can perturb BMSCs\u2019 differential potential via the paracrine signaling of SASP, which was also demonstrated by in vivo experiments. In conclusion, we identified the SASP factor partially responsible for the degenerative differentiation of BMSCs, which allowed us to hypothesize that senescent osteocytes and their SASPs may contribute to radiation-induced bone loss.<\/jats:p>","DOI":"10.3390\/ijms22179323","type":"journal-article","created":{"date-parts":[[2021,8,29]],"date-time":"2021-08-29T21:45:16Z","timestamp":1630273516000},"page":"9323","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Radiation-Induced Osteocyte Senescence Alters Bone Marrow Mesenchymal Stem Cell Differentiation Potential via Paracrine Signaling"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9911-7588","authenticated-orcid":false,"given":"Linshan","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Radiological Hygiene, Institute of Radiation Medicine, Fudan University, 2094 Xietu Road, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuyang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Radiological Hygiene, Institute of Radiation Medicine, Fudan University, 2094 Xietu Road, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianping","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Radiological Hygiene, Institute of Radiation Medicine, Fudan University, 2094 Xietu Road, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianglong","family":"Zhai","sequence":"additional","affiliation":[{"name":"Department of Radiological Hygiene, Institute of Radiation Medicine, Fudan University, 2094 Xietu Road, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6481-0713","authenticated-orcid":false,"given":"Li","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Radiological Hygiene, Institute of Radiation Medicine, Fudan University, 2094 Xietu Road, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5637-5184","authenticated-orcid":false,"given":"Guoying","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Radiological Hygiene, Institute of Radiation Medicine, Fudan University, 2094 Xietu Road, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"a025163","DOI":"10.1101\/cshperspect.a025163","article-title":"The emergence of geroscience as an interdisciplinary approach to the enhancement of health span and life span","volume":"6","author":"Sierra","year":"2016","journal-title":"Cold Spring Harb. 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