CYTL1 regulates bone homeostasis in mice by modulating osteogenesis of mesenchymal stem cells and osteoclastogenesis of bone marrow-derived macrophages
| Autor: | Jang-Soo Chun, Youngnim Shin, Jeong-In Yang, Yoonkyung Won |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Cancer Research medicine.medical_treatment Immunology Article Bone and Bones Bone resorption Mice 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Osteogenesis Osteoclast medicine Animals Homeostasis Humans RNA Messenger lcsh:QH573-671 Bone Resorption Endochondral ossification Mice Knockout lcsh:Cytology Chemistry Macrophages Mesenchymal stem cell Cell Differentiation Mesenchymal Stem Cells Blood Proteins Cell Biology Cell biology Mice Inbred C57BL RUNX2 030104 developmental biology medicine.anatomical_structure Cytokine 030220 oncology & carcinogenesis Cytokines Bone marrow Stem cell |
| Zdroj: | Cell Death & Disease Cell Death and Disease, Vol 10, Iss 2, Pp 1-13 (2019) |
| ISSN: | 2041-4889 |
| Popis: | We previously showed that mice with knockout of Cytl1, a functionally uncharacterized cytokine candidate, exhibit normal endochondral ossification and long-bone development. Here, we investigated the potential functions of CYTL1 in bone homeostasis. We found that Cytl1−/− mice exhibited higher bone mass than wild-type littermates and resisted ovariectomy-induced bone resorption. This led us to investigate the functions of CYTL1 in the osteogenesis and osteoclastogenesis of bone marrow-derived stem cells. CYTL1 was down-regulated during the osteogenesis of human mesenchymal stem cells (hMSCs). The osteogenesis of hMSCs was inhibited by overexpression or exogenous treatment of CYTL1, but enhanced by CYTL1 knockdown. CYTL1 decreased osteogenesis by inhibiting RUNX2 and promoted proliferation among undifferentiated hMSCs, but stimulated apoptosis among osteogenically differentiating cells. Finally, Cytl1−/− mice exhibited inhibition of osteoclast activity and the osteoclastogenesis of bone marrow-derived macrophages. Our results collectively suggest that CYTL1 negatively regulates the osteogenesis of MSCs and positively regulates osteoclastogenesis to modulate bone mass in mice. |
| Databáze: | OpenAIRE |
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