Mechanical Unloading Promotes Osteoclastic Differentiation and Bone Resorption by Modulating the MSC Secretome to Favor Inflammation
Aging, space flight, and prolonged bed rest have all been linked to bone loss, and no effective treatments are clinically available at present. Here, with the rodent hindlimb unloading (HU) model, we report that the bone marrow (BM) microenvironment was significantly altered, with an increased numbe...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2024-03-01
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| Series: | Cell Transplantation |
| Online Access: | https://doi.org/10.1177/09636897241236584 |
| _version_ | 1797255693930070016 |
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| author | Wanyuji Wang Xueling Zheng Hehe Wang Bin Zuo Sisi Chen Jiao Li |
| author_facet | Wanyuji Wang Xueling Zheng Hehe Wang Bin Zuo Sisi Chen Jiao Li |
| author_sort | Wanyuji Wang |
| collection | DOAJ |
| description | Aging, space flight, and prolonged bed rest have all been linked to bone loss, and no effective treatments are clinically available at present. Here, with the rodent hindlimb unloading (HU) model, we report that the bone marrow (BM) microenvironment was significantly altered, with an increased number of myeloid cells and elevated inflammatory cytokines. In such inflammatory BM, the osteoclast-mediated bone resorption was greatly enhanced, leading to a shifted bone remodeling balance that ultimately ends up with disuse-induced osteoporosis. Using Piezo1 conditional knockout (KO) mice (Piezo1 fl/fl ;LepRCre), we proved that lack of mechanical stimuli on LepR + mesenchymal stem cells (MSCs) is the main reason for the pathological BM inflammation. Mechanically, the secretome of MSCs was regulated by mechanical stimuli. Inadequate mechanical load leads to increased production of inflammatory cytokines, such as interleukin (IL)-1α, IL-6, macrophage colony-stimulating factor 1 (M-CSF-1), and so on, which promotes monocyte proliferation and osteoclastic differentiation. Interestingly, transplantation of 10% cyclic mechanical stretch (CMS)-treated MSCs into HU animals significantly alleviated the BM microenvironment and rebalanced bone remodeling. In summary, our research revealed a new mechanism underlying mechanical unloading-induced bone loss and suggested a novel stem cell-based therapy to potentially prevent disuse-induced osteoporosis. |
| first_indexed | 2024-04-24T22:09:55Z |
| format | Article |
| id | doaj.art-00ceb6572a184c93842373b894a1a398 |
| institution | Directory Open Access Journal |
| issn | 1555-3892 |
| language | English |
| last_indexed | 2024-04-24T22:09:55Z |
| publishDate | 2024-03-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Cell Transplantation |
| spelling | doaj.art-00ceb6572a184c93842373b894a1a3982024-03-20T10:03:33ZengSAGE PublishingCell Transplantation1555-38922024-03-013310.1177/09636897241236584Mechanical Unloading Promotes Osteoclastic Differentiation and Bone Resorption by Modulating the MSC Secretome to Favor InflammationWanyuji Wang0Xueling Zheng1Hehe Wang2Bin Zuo3Sisi Chen4Jiao Li5Department of Cell Biology, Zunyi Medical University, Zunyi, ChinaDepartment of Cell Biology, Zunyi Medical University, Zunyi, ChinaDepartment of Cell Biology, Zunyi Medical University, Zunyi, ChinaDepartment of Orthopedic Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Orthopedic Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Cell Biology, Zunyi Medical University, Zunyi, ChinaAging, space flight, and prolonged bed rest have all been linked to bone loss, and no effective treatments are clinically available at present. Here, with the rodent hindlimb unloading (HU) model, we report that the bone marrow (BM) microenvironment was significantly altered, with an increased number of myeloid cells and elevated inflammatory cytokines. In such inflammatory BM, the osteoclast-mediated bone resorption was greatly enhanced, leading to a shifted bone remodeling balance that ultimately ends up with disuse-induced osteoporosis. Using Piezo1 conditional knockout (KO) mice (Piezo1 fl/fl ;LepRCre), we proved that lack of mechanical stimuli on LepR + mesenchymal stem cells (MSCs) is the main reason for the pathological BM inflammation. Mechanically, the secretome of MSCs was regulated by mechanical stimuli. Inadequate mechanical load leads to increased production of inflammatory cytokines, such as interleukin (IL)-1α, IL-6, macrophage colony-stimulating factor 1 (M-CSF-1), and so on, which promotes monocyte proliferation and osteoclastic differentiation. Interestingly, transplantation of 10% cyclic mechanical stretch (CMS)-treated MSCs into HU animals significantly alleviated the BM microenvironment and rebalanced bone remodeling. In summary, our research revealed a new mechanism underlying mechanical unloading-induced bone loss and suggested a novel stem cell-based therapy to potentially prevent disuse-induced osteoporosis.https://doi.org/10.1177/09636897241236584 |
| spellingShingle | Wanyuji Wang Xueling Zheng Hehe Wang Bin Zuo Sisi Chen Jiao Li Mechanical Unloading Promotes Osteoclastic Differentiation and Bone Resorption by Modulating the MSC Secretome to Favor Inflammation Cell Transplantation |
| title | Mechanical Unloading Promotes Osteoclastic Differentiation and Bone Resorption by Modulating the MSC Secretome to Favor Inflammation |
| title_full | Mechanical Unloading Promotes Osteoclastic Differentiation and Bone Resorption by Modulating the MSC Secretome to Favor Inflammation |
| title_fullStr | Mechanical Unloading Promotes Osteoclastic Differentiation and Bone Resorption by Modulating the MSC Secretome to Favor Inflammation |
| title_full_unstemmed | Mechanical Unloading Promotes Osteoclastic Differentiation and Bone Resorption by Modulating the MSC Secretome to Favor Inflammation |
| title_short | Mechanical Unloading Promotes Osteoclastic Differentiation and Bone Resorption by Modulating the MSC Secretome to Favor Inflammation |
| title_sort | mechanical unloading promotes osteoclastic differentiation and bone resorption by modulating the msc secretome to favor inflammation |
| url | https://doi.org/10.1177/09636897241236584 |
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