Stromal Lineage Precursors from Rodent Femur and Tibia Bone Marrows after Hindlimb Unloading: Functional Ex Vivo Analysis
Rodent hindlimb unloading (HU) model was developed to elucidate responses/mechanisms of adverse consequences of space weightlessness. Multipotent mesenchymal stromal cells (MMSCs) were isolated from rat femur and tibia bone marrows and examined ex vivo after 2 weeks of HU and subsequent 2 weeks of r...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-05-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/10/8594 |
| _version_ | 1797599894064594944 |
|---|---|
| author | Elena Markina Elena Andreeva Ludmila Buravkova |
| author_facet | Elena Markina Elena Andreeva Ludmila Buravkova |
| author_sort | Elena Markina |
| collection | DOAJ |
| description | Rodent hindlimb unloading (HU) model was developed to elucidate responses/mechanisms of adverse consequences of space weightlessness. Multipotent mesenchymal stromal cells (MMSCs) were isolated from rat femur and tibia bone marrows and examined ex vivo after 2 weeks of HU and subsequent 2 weeks of restoration of load (HU + RL). In both bones, decrease of fibroblast colony forming units (CFU-f) after HU with restoration after HU + RL detected. In CFU-f and MMSCs, levels of spontaneous/induced osteocommitment were similar. MMSCs from tibia initially had greater spontaneous mineralization of extracellular matrix but were less sensitive to osteoinduction. There was no recovery of initial levels of mineralization in MMSCs from both bones during HU + RL. After HU, most bone-related genes were downregulated in tibia or femur MMSCs. After HU + RL, the initial level of transcription was restored in femur, while downregulation persisted in tibia MMSCs. Therefore, HU provoked a decrease of osteogenic activity of BM stromal precursors at transcriptomic and functional levels. Despite unidirectionality of changes, the negative effects of HU were more pronounced in stromal precursors from distal limb—tibia. These observations appear to be on demand for elucidation of mechanisms of skeletal disorders in astronauts in prospect of long-term space missions. |
| first_indexed | 2024-03-11T03:40:47Z |
| format | Article |
| id | doaj.art-a18c7c38da8c4b8b931df115bc2bad9d |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T03:40:47Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-a18c7c38da8c4b8b931df115bc2bad9d2023-11-18T01:38:26ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-05-012410859410.3390/ijms24108594Stromal Lineage Precursors from Rodent Femur and Tibia Bone Marrows after Hindlimb Unloading: Functional Ex Vivo AnalysisElena Markina0Elena Andreeva1Ludmila Buravkova2Institute of Biomedical Problems, Russian Academy of Sciences, 123007 Moscow, RussiaInstitute of Biomedical Problems, Russian Academy of Sciences, 123007 Moscow, RussiaInstitute of Biomedical Problems, Russian Academy of Sciences, 123007 Moscow, RussiaRodent hindlimb unloading (HU) model was developed to elucidate responses/mechanisms of adverse consequences of space weightlessness. Multipotent mesenchymal stromal cells (MMSCs) were isolated from rat femur and tibia bone marrows and examined ex vivo after 2 weeks of HU and subsequent 2 weeks of restoration of load (HU + RL). In both bones, decrease of fibroblast colony forming units (CFU-f) after HU with restoration after HU + RL detected. In CFU-f and MMSCs, levels of spontaneous/induced osteocommitment were similar. MMSCs from tibia initially had greater spontaneous mineralization of extracellular matrix but were less sensitive to osteoinduction. There was no recovery of initial levels of mineralization in MMSCs from both bones during HU + RL. After HU, most bone-related genes were downregulated in tibia or femur MMSCs. After HU + RL, the initial level of transcription was restored in femur, while downregulation persisted in tibia MMSCs. Therefore, HU provoked a decrease of osteogenic activity of BM stromal precursors at transcriptomic and functional levels. Despite unidirectionality of changes, the negative effects of HU were more pronounced in stromal precursors from distal limb—tibia. These observations appear to be on demand for elucidation of mechanisms of skeletal disorders in astronauts in prospect of long-term space missions.https://www.mdpi.com/1422-0067/24/10/8594microgravity simulationhindlimb unloadingtibiafemurbone marrowmultipotent mesenchymal stromal cells |
| spellingShingle | Elena Markina Elena Andreeva Ludmila Buravkova Stromal Lineage Precursors from Rodent Femur and Tibia Bone Marrows after Hindlimb Unloading: Functional Ex Vivo Analysis International Journal of Molecular Sciences microgravity simulation hindlimb unloading tibia femur bone marrow multipotent mesenchymal stromal cells |
| title | Stromal Lineage Precursors from Rodent Femur and Tibia Bone Marrows after Hindlimb Unloading: Functional Ex Vivo Analysis |
| title_full | Stromal Lineage Precursors from Rodent Femur and Tibia Bone Marrows after Hindlimb Unloading: Functional Ex Vivo Analysis |
| title_fullStr | Stromal Lineage Precursors from Rodent Femur and Tibia Bone Marrows after Hindlimb Unloading: Functional Ex Vivo Analysis |
| title_full_unstemmed | Stromal Lineage Precursors from Rodent Femur and Tibia Bone Marrows after Hindlimb Unloading: Functional Ex Vivo Analysis |
| title_short | Stromal Lineage Precursors from Rodent Femur and Tibia Bone Marrows after Hindlimb Unloading: Functional Ex Vivo Analysis |
| title_sort | stromal lineage precursors from rodent femur and tibia bone marrows after hindlimb unloading functional ex vivo analysis |
| topic | microgravity simulation hindlimb unloading tibia femur bone marrow multipotent mesenchymal stromal cells |
| url | https://www.mdpi.com/1422-0067/24/10/8594 |
| work_keys_str_mv | AT elenamarkina stromallineageprecursorsfromrodentfemurandtibiabonemarrowsafterhindlimbunloadingfunctionalexvivoanalysis AT elenaandreeva stromallineageprecursorsfromrodentfemurandtibiabonemarrowsafterhindlimbunloadingfunctionalexvivoanalysis AT ludmilaburavkova stromallineageprecursorsfromrodentfemurandtibiabonemarrowsafterhindlimbunloadingfunctionalexvivoanalysis |