Hedgehog signaling directs cell differentiation and plays a critical role in tendon enthesis healing
Abstract A high prevalence of rotator cuff tears presents a major clinical challenge. A better understanding of the molecular mechanisms underlying enthesis development and healing is needed for developing treatments. We recently identified hedgehog (Hh)-lineage cells critical for enthesis developme...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | npj Regenerative Medicine |
| Online Access: | https://doi.org/10.1038/s41536-025-00392-4 |
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| author | Fei Fang Matthew Casserly Julia Robbins Stavros Thomopoulos |
| author_facet | Fei Fang Matthew Casserly Julia Robbins Stavros Thomopoulos |
| author_sort | Fei Fang |
| collection | DOAJ |
| description | Abstract A high prevalence of rotator cuff tears presents a major clinical challenge. A better understanding of the molecular mechanisms underlying enthesis development and healing is needed for developing treatments. We recently identified hedgehog (Hh)-lineage cells critical for enthesis development and repair. This study revealed cell-cell communication within the Hh-lineage cell population. To further characterize the role of Hh signaling, we used mouse models to activate and inactivate the Hh pathway in enthesis progenitors. Activation of Hh target genes during enthesis development increased its mineralization and mechanical properties. Activation of Hh signaling at the injured mature enthesis promoted fibrocartilage formation, enhanced mineralization, and increased expression of chondrogenic and osteogenic markers, which implies that Hh signaling drives cell differentiation to regenerate the damaged enthesis. Conversely, deletion of Hh target genes impaired enthesis healing. In summary, this study revealed a new strategy for enthesis repair via activation of Hh signaling in endogenous cells. |
| format | Article |
| id | doaj-art-2dc8beb71b29443983bd6452cee50cd0 |
| institution | Kabale University |
| issn | 2057-3995 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Regenerative Medicine |
| spelling | doaj-art-2dc8beb71b29443983bd6452cee50cd02025-01-26T12:19:06ZengNature Portfolionpj Regenerative Medicine2057-39952025-01-0110111010.1038/s41536-025-00392-4Hedgehog signaling directs cell differentiation and plays a critical role in tendon enthesis healingFei Fang0Matthew Casserly1Julia Robbins2Stavros Thomopoulos3Leni and Peter W. May Department of Orthopaedics, Icahn School of Medicine at Mount SinaiLeni and Peter W. May Department of Orthopaedics, Icahn School of Medicine at Mount SinaiLeni and Peter W. May Department of Orthopaedics, Icahn School of Medicine at Mount SinaiDepartment of Orthopedic Surgery, Columbia UniversityAbstract A high prevalence of rotator cuff tears presents a major clinical challenge. A better understanding of the molecular mechanisms underlying enthesis development and healing is needed for developing treatments. We recently identified hedgehog (Hh)-lineage cells critical for enthesis development and repair. This study revealed cell-cell communication within the Hh-lineage cell population. To further characterize the role of Hh signaling, we used mouse models to activate and inactivate the Hh pathway in enthesis progenitors. Activation of Hh target genes during enthesis development increased its mineralization and mechanical properties. Activation of Hh signaling at the injured mature enthesis promoted fibrocartilage formation, enhanced mineralization, and increased expression of chondrogenic and osteogenic markers, which implies that Hh signaling drives cell differentiation to regenerate the damaged enthesis. Conversely, deletion of Hh target genes impaired enthesis healing. In summary, this study revealed a new strategy for enthesis repair via activation of Hh signaling in endogenous cells.https://doi.org/10.1038/s41536-025-00392-4 |
| spellingShingle | Fei Fang Matthew Casserly Julia Robbins Stavros Thomopoulos Hedgehog signaling directs cell differentiation and plays a critical role in tendon enthesis healing npj Regenerative Medicine |
| title | Hedgehog signaling directs cell differentiation and plays a critical role in tendon enthesis healing |
| title_full | Hedgehog signaling directs cell differentiation and plays a critical role in tendon enthesis healing |
| title_fullStr | Hedgehog signaling directs cell differentiation and plays a critical role in tendon enthesis healing |
| title_full_unstemmed | Hedgehog signaling directs cell differentiation and plays a critical role in tendon enthesis healing |
| title_short | Hedgehog signaling directs cell differentiation and plays a critical role in tendon enthesis healing |
| title_sort | hedgehog signaling directs cell differentiation and plays a critical role in tendon enthesis healing |
| url | https://doi.org/10.1038/s41536-025-00392-4 |
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