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Here, changes in gene expression due to long\u2010term mechanical stress were analyzed using RNA\u2010seq in a rabbit LF hypertrophy model. In combination with previously reported analysis results, periostin was identified as a molecule whose expression fluctuates due to mechanical stress. The expression and function of periostin were further investigated using human LF tissues and primary LF cell cultures. Periostin was abundantly expressed in human hypertrophied LF tissues, and periostin gene expression was significantly correlated with LF thickness. In vitro, mechanical stress increased gene expressions of periostin, transforming growth factor\u2010\u03b21, \u03b1\u2010smooth muscle actin, collagen type 1 alpha 1, and interleukin\u20106 (IL\u20106) in LF cells. Periostin blockade suppressed the mechanical stress\u2010induced gene expression of IL\u20106 while periostin treatment increased IL\u20106 gene expression. Our results suggest that periostin is upregulated by mechanical stress and promotes inflammation by upregulating IL\u20106 expression, which leads to LF degeneration and hypertrophy. Periostin may be a pivotal molecule for LF hypertrophy and a promising therapeutic target for lumbar spinal stenosis.<\/jats:p>","DOI":"10.1096\/fj.202200917rr","type":"journal-article","created":{"date-parts":[[2022,12,30]],"date-time":"2022-12-30T10:31:05Z","timestamp":1672396265000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Periostin increased by mechanical stress upregulates interleukin\u20106 expression in the ligamentum flavum"],"prefix":"10.1096","volume":"37","author":[{"given":"Akito","family":"Yabu","sequence":"first","affiliation":[{"name":"Department of Orthopedic Surgery Osaka City University Graduate School of Medicine  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4800-9226","authenticated-orcid":false,"given":"Akinobu","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Osaka 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