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The\n                    <jats:italic>hedgehog<\/jats:italic>\n                    gene was first discovered in\n                    <jats:italic>Drosophila\u2009melanogaster<\/jats:italic>\n                    , and the pathway is evolutionarily conserved in most animals. Although there are several hedgehog ligands with different protein expression patterns, they share a common plasma membrane receptor, Patched1 and hedgehog signalling pathway activation is transduced through the G\u2010protein\u2010coupled receptor\u2010like protein Smoothened (SMO) and downstream effectors. Functional assays revealed that activation of SMO is dependent on sterol binding, and cholesterol was observed bound to SMO in crystallography experiments. In vertebrates, hedgehog signalling coordinates endochondral ossification and balances osteoblast and osteoclast activation to maintain homeostasis. A recently discovered mutation of SMO in humans (\n                    <jats:italic>\n                      SMO\n                      <jats:sup>R173C<\/jats:sup>\n                    <\/jats:italic>\n                    ) is predicted to alter cholesterol binding and is associated with a higher risk of hip OA. Functional studies in mice and human tissue analysis provide evidence that hedgehog signalling is pathologically activated in chondrocytes of osteoarthritic cartilage.\n                  <\/jats:p>","DOI":"10.1111\/febs.16440","type":"journal-article","created":{"date-parts":[[2022,3,19]],"date-time":"2022-03-19T09:33:33Z","timestamp":1647682413000},"page":"3059-3075","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Hedgehog signalling in bone and osteoarthritis: the role of Smoothened and cholesterol"],"prefix":"10.1111","volume":"290","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4402-8959","authenticated-orcid":false,"given":"Abbi Elise","family":"Smith","sequence":"first","affiliation":[{"name":"Faculty of Medicine Department of Biochemistry and Molecular Biology University of Iceland  Reykjavik 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