Polycystin-1 regulates tendon-derived mesenchymal stem cells fate and matrix organization in heterotopic ossification
Abstract Mechanical stress modulates bone formation and organization of the extracellular matrix (ECM), the interaction of which affects heterotopic ossification (HO). However, the mechanically sensitive cell populations in HO and the underlying mechanism remain elusive. Here, we show that the mecha...
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Nature Publishing Group
2025-01-01
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| Series: | Bone Research |
| Online Access: | https://doi.org/10.1038/s41413-024-00392-y |
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| author | Yi Li Xu Mei Huang Yang Zhang Xin Ying Su Min Huang Nan Yu Zou Yu Rui Jiao Yu Chen Sun Ling Liu Yong Hua Lei Chang Jun Li |
| author_facet | Yi Li Xu Mei Huang Yang Zhang Xin Ying Su Min Huang Nan Yu Zou Yu Rui Jiao Yu Chen Sun Ling Liu Yong Hua Lei Chang Jun Li |
| author_sort | Yi Li Xu |
| collection | DOAJ |
| description | Abstract Mechanical stress modulates bone formation and organization of the extracellular matrix (ECM), the interaction of which affects heterotopic ossification (HO). However, the mechanically sensitive cell populations in HO and the underlying mechanism remain elusive. Here, we show that the mechanical protein Polysyctin-1 (PC1, Pkd1) regulates CTSK lineage tendon-derived mesenchymal stem cell (TDMSC) fate and ECM organization, thus affecting HO progression. First, we revealed that CTSK lineage TDMSCs are the major source of osteoblasts and fibroblasts in HO and are responsive to mechanical cues via single-cell RNA sequencing analysis and experiments with a lineage tracing mouse model. Moreover, we showed that PC1 mediates the mechanosignal transduction of CTSK lineage TDMSCs to regulate osteogenic and fibrogenic differentiation and alters the ECM architecture by facilitating TAZ nuclear translocation. Conditional gene depletion of Pkd1 or Taz in CTSK lineage cells and pharmaceutical intervention in the PC1-TAZ axis disrupt osteogenesis, fibrogenesis and ECM organization, and consequently attenuate HO progression. These findings suggest that mechanically sensitive CTSK-lineage TDMSCs contribute to heterotopic ossification through PC1-TAZ signaling axis mediated cell fate determination and ECM organization. |
| format | Article |
| id | doaj-art-62c10e5b907c47839809fcadb7c30964 |
| institution | Kabale University |
| issn | 2095-6231 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Bone Research |
| spelling | doaj-art-62c10e5b907c47839809fcadb7c309642025-01-26T12:19:50ZengNature Publishing GroupBone Research2095-62312025-01-0113111410.1038/s41413-024-00392-yPolycystin-1 regulates tendon-derived mesenchymal stem cells fate and matrix organization in heterotopic ossificationYi Li Xu0Mei Huang1Yang Zhang2Xin Ying Su3Min Huang4Nan Yu Zou5Yu Rui Jiao6Yu Chen Sun7Ling Liu8Yong Hua Lei9Chang Jun Li10Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital of Central South UniversityDepartment of Endocrinology, Endocrinology Research Center, Xiangya Hospital of Central South UniversityXiangya School of Medicine, Central South UniversityDepartment of Orthodontics, Xiangya Hospital, Central South UniversityDepartment of Endocrinology, Endocrinology Research Center, Xiangya Hospital of Central South UniversityDepartment of Endocrinology, Endocrinology Research Center, Xiangya Hospital of Central South UniversityDepartment of Endocrinology, Endocrinology Research Center, Xiangya Hospital of Central South UniversityDepartment of Endocrinology, Endocrinology Research Center, Xiangya Hospital of Central South UniversityDepartment of Endocrinology, Endocrinology Research Center, Xiangya Hospital of Central South UniversityDepartment of Orthodontics, Xiangya Hospital, Central South UniversityDepartment of Endocrinology, Endocrinology Research Center, Xiangya Hospital of Central South UniversityAbstract Mechanical stress modulates bone formation and organization of the extracellular matrix (ECM), the interaction of which affects heterotopic ossification (HO). However, the mechanically sensitive cell populations in HO and the underlying mechanism remain elusive. Here, we show that the mechanical protein Polysyctin-1 (PC1, Pkd1) regulates CTSK lineage tendon-derived mesenchymal stem cell (TDMSC) fate and ECM organization, thus affecting HO progression. First, we revealed that CTSK lineage TDMSCs are the major source of osteoblasts and fibroblasts in HO and are responsive to mechanical cues via single-cell RNA sequencing analysis and experiments with a lineage tracing mouse model. Moreover, we showed that PC1 mediates the mechanosignal transduction of CTSK lineage TDMSCs to regulate osteogenic and fibrogenic differentiation and alters the ECM architecture by facilitating TAZ nuclear translocation. Conditional gene depletion of Pkd1 or Taz in CTSK lineage cells and pharmaceutical intervention in the PC1-TAZ axis disrupt osteogenesis, fibrogenesis and ECM organization, and consequently attenuate HO progression. These findings suggest that mechanically sensitive CTSK-lineage TDMSCs contribute to heterotopic ossification through PC1-TAZ signaling axis mediated cell fate determination and ECM organization.https://doi.org/10.1038/s41413-024-00392-y |
| spellingShingle | Yi Li Xu Mei Huang Yang Zhang Xin Ying Su Min Huang Nan Yu Zou Yu Rui Jiao Yu Chen Sun Ling Liu Yong Hua Lei Chang Jun Li Polycystin-1 regulates tendon-derived mesenchymal stem cells fate and matrix organization in heterotopic ossification Bone Research |
| title | Polycystin-1 regulates tendon-derived mesenchymal stem cells fate and matrix organization in heterotopic ossification |
| title_full | Polycystin-1 regulates tendon-derived mesenchymal stem cells fate and matrix organization in heterotopic ossification |
| title_fullStr | Polycystin-1 regulates tendon-derived mesenchymal stem cells fate and matrix organization in heterotopic ossification |
| title_full_unstemmed | Polycystin-1 regulates tendon-derived mesenchymal stem cells fate and matrix organization in heterotopic ossification |
| title_short | Polycystin-1 regulates tendon-derived mesenchymal stem cells fate and matrix organization in heterotopic ossification |
| title_sort | polycystin 1 regulates tendon derived mesenchymal stem cells fate and matrix organization in heterotopic ossification |
| url | https://doi.org/10.1038/s41413-024-00392-y |
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