Osteoclast-derived exosomal let-7a-5p targets Smad2 to promote the hypertrophic differentiation of chondrocytes
| Autor: | Mengmeng Liang, Shiwu Dong, Rui Dong, Zhiyong Hou, Yun Bai, Jianmei Li, Fei Kang, Xinyun Han, Xiaoshan Gong, Fanchun Zeng, Jingjin Dai |
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| Rok vydání: | 2020 |
| Předmět: |
musculoskeletal diseases
0301 basic medicine Physiology Chemistry Cartilage Chondrocyte hypertrophy Cell Biology Microvesicles Cell biology 03 medical and health sciences 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure Osteoclast 030220 oncology & carcinogenesis microRNA medicine Bone marrow Endochondral ossification Intracellular |
| Zdroj: | American Journal of Physiology-Cell Physiology. 319:C21-C33 |
| ISSN: | 1522-1563 0363-6143 |
| DOI: | 10.1152/ajpcell.00039.2020 |
| Popis: | The invasion of osteoclasts into the cartilage via blood vessels advances the process of endochondral ossification, and dysregulation of dynamic intercellular interactions results in skeletal dysplasias. Although the regulation of osteoclasts by growth plate chondrocytes has been reported in detail, the effect of osteoclasts on chondrocytes remains to be determined. In this study, ATDC5 cells and bone marrow mesenchymal stem cells were differentiated into chondrocytes and treated with conditioned medium obtained from bone marrow macrophages differentiated to osteoclast precursors and osteoclasts. Exosomes were inhibited in conditioned medium or isolated directly from osteoclasts to further determine whether osteoclast-derived exosomes play an important role in chondrocyte hypertrophy. Additionally, exosomal miRNAs were detected, and let-7a-5p was selected as an miRNA with significantly increased expression in osteoclast-derived exosomes. Experiments were performed to verify the potential target Smad2 and investigate how let-7a-5p affected chondrocytes. The results suggest that both osteoclast precursors and osteoclasts promote chondrocyte hypertrophy and that the promotive effect of osteoclasts is more significant than that of osteoclast precursors. Osteoclast-derived exosomes promote the hypertrophic differentiation of chondrocytes. Moreover, osteoclast-derived exosomal let-7a-5p inhibits Smad2 to decrease the transforming growth factor-β-induced inhibition of chondrocyte hypertrophy. Our research reveals the role of osteoclasts in the regulation of chondrocytes and provides insights into the highly coordinated intercellular process of endochondral ossification. |
| Databáze: | OpenAIRE |
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