{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T05:19:15Z","timestamp":1787635155347,"version":"build-2736575974"},"reference-count":49,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T00:00:00Z","timestamp":1787356800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging of the National Institutes of Health","doi-asserted-by":"publisher","award":["R01AG070079"],"award-info":[{"award-number":["R01AG070079"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"crossref","award":["R01AR077145"],"award-info":[{"award-number":["R01AR077145"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"crossref"}]},{"award":["R01AR077145"],"award-info":[{"award-number":["R01AR077145"]}],"id":[{"id":"https:\/\/ror.org\/006zn3t30","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000052","name":"Office of the Director of the National Institutes of Health","doi-asserted-by":"publisher","award":["S10OD026763"],"award-info":[{"award-number":["S10OD026763"]}],"id":[{"id":"10.13039\/100000052","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Sonic hedgehog (SHH) expression by nucleus pulposus (NP) cells is important for intervertebral disc development and maintenance. The lumbosacral disc, the most immobile region of the spine, lies adjacent to the sacrum and is most vulnerable to degeneration. We hypothesized that a lack of mobility represses SHH expression by NP cells, leading to degenerative changes in the intervertebral disc. To test this hypothesis, we employed a Shh-LacZ reporter mouse and a tail-loop surgical model of constant compression and immobility. Using a comprehensive level-by-level analysis, we first determined the coccygeal level most affected by geometric and histopathological changes. We next determined the effects of constant compression and immobility on the subset of SHH-expressing cells compared with sham controls. Multiplex qPCR analysis validated a decline in Shh and its target Gli1 expression by NP cells in the tail-looped discs that was associated with an increase in Piezo1 expression compared to sham controls. In summary, the findings support a model in which restricted mobility and sustained compression in lumbosacral discs accelerate pathology by prematurely silencing developmental signaling programs, such as SHH, required for NP homeostasis.<\/jats:p>","DOI":"10.3390\/cells15171506","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T08:03:41Z","timestamp":1787558621000},"page":"1506","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mechanical Suppression of Sonic Hedgehog Signaling by Nucleus Pulposus Cells Underlies Early Disc Degeneration in Mouse"],"prefix":"10.3390","volume":"15","author":[{"given":"Sohrab","family":"Virk","sequence":"first","affiliation":[{"name":"Spine Service, Hospital for Special Surgery, New York, NY 10021, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veeraj","family":"Shah","sequence":"additional","affiliation":[{"name":"Orthopedic Soft Tissue Research Program, Hospital for Special Surgery, New York, NY 10021, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1753-8301","authenticated-orcid":false,"given":"Vikrant","family":"Piprode","sequence":"additional","affiliation":[{"name":"Orthopedic Soft Tissue Research Program, Hospital for Special Surgery, New York, NY 10021, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire Marie","family":"Kemp","sequence":"additional","affiliation":[{"name":"Orthopedic Soft Tissue Research Program, Hospital for Special Surgery, New York, NY 10021, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harshith","family":"Alluri","sequence":"additional","affiliation":[{"name":"Orthopedic Soft Tissue Research Program, Hospital for Special Surgery, New York, NY 10021, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6098-9998","authenticated-orcid":false,"given":"Kathleen F.","family":"Vincent","sequence":"additional","affiliation":[{"name":"Orthopedic Soft Tissue Research Program, Hospital for Special Surgery, New York, NY 10021, USA"},{"name":"Department of Cell and Developmental Biology, Weill Cornell Medical College, New York, NY 10021, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravi","family":"Krishnan","sequence":"additional","affiliation":[{"name":"Orthopedic Soft Tissue Research Program, Hospital for Special Surgery, New York, NY 10021, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4025-5980","authenticated-orcid":false,"given":"Justin","family":"Hong","sequence":"additional","affiliation":[{"name":"Orthopedic Soft Tissue Research Program, Hospital for Special Surgery, New York, NY 10021, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd J.","family":"Albert","sequence":"additional","affiliation":[{"name":"Spine Service, Hospital for Special Surgery, New York, NY 10021, USA"},{"name":"Weill Cornell Medical College, New York, NY 10021, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3683-9791","authenticated-orcid":false,"given":"Chitra L.","family":"Dahia","sequence":"additional","affiliation":[{"name":"Orthopedic Soft Tissue Research Program, Hospital for Special Surgery, New York, NY 10021, USA"},{"name":"Department of Cell and Developmental Biology, Weill Cornell Medical College, New York, NY 10021, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2356","DOI":"10.1016\/S0140-6736(18)30480-X","article-title":"What low back pain is and why we need to pay attention","volume":"391","author":"Hartvigsen","year":"2018","journal-title":"Lancet"},{"key":"ref_2","unstructured":"(2023). 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