Myostatin Promotes Osteoclastogenesis by Regulating Ccdc50 Gene Expression and RANKL-Induced NF-κB and MAPK Pathways
Myostatin is a crucial cytokine that is widely present in skeletal muscle and that negatively regulates the growth and development of muscle cells. Recent research has shown that myostatin might play an essential role in bone metabolism. In RAW264.7 cells and bone marrow monocytes (BMMCs), myostatin...
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Frontiers Media S.A.
2020-11-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2020.565163/full |
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| author | Xin Zhi Qian Chen Shaojun Song Zhengrong Gu Wenqiang Wei Huiwen Chen Xiao Chen Weizong Weng Qirong Zhou Jin Cui Liehu Cao |
| author_facet | Xin Zhi Qian Chen Shaojun Song Zhengrong Gu Wenqiang Wei Huiwen Chen Xiao Chen Weizong Weng Qirong Zhou Jin Cui Liehu Cao |
| author_sort | Xin Zhi |
| collection | DOAJ |
| description | Myostatin is a crucial cytokine that is widely present in skeletal muscle and that negatively regulates the growth and development of muscle cells. Recent research has shown that myostatin might play an essential role in bone metabolism. In RAW264.7 cells and bone marrow monocytes (BMMCs), myostatin activates the expression of the II type receptor ActR II B. Here, we report that myostatin significantly promoted RANKL/M-CSF-induced osteoclastogenesis and activated NF-κB and MAPK pathways in vitro via the Ccdc50 gene. Overexpression of myostatin promoted osteoclastogenesis and osteoclastogenesis-related markers including c-Src, MMP9, CTR, CK, and NFATc1. Specifically, myostatin increased the phosphorylation of Smad2, which led to the activation of NF-κB and MAPK pathways to activate osteoclastogenesis. Ccdc50 was identified as a gene whose expression was highly decreased in osteoclastogenesis upon myostatin treatment, and it could inhibit the function of myostatin in osteoclastogenesis by blocking NF-κB and MAPKs pathways. Our study indicates that myostatin is a promising candidate target for inhibiting RANKL-mediated osteoclastogenesis and might participate in therapy for osteoporosis, and that the Ccdc50 gene plays a significant role in the regulatory process. |
| first_indexed | 2024-12-18T23:15:38Z |
| format | Article |
| id | doaj.art-83e7b4557f6045c784db2c8b7f24b605 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-18T23:15:38Z |
| publishDate | 2020-11-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-83e7b4557f6045c784db2c8b7f24b6052022-12-21T20:48:14ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122020-11-011110.3389/fphar.2020.565163565163Myostatin Promotes Osteoclastogenesis by Regulating Ccdc50 Gene Expression and RANKL-Induced NF-κB and MAPK PathwaysXin Zhi0Qian Chen1Shaojun Song2Zhengrong Gu3Wenqiang Wei4Huiwen Chen5Xiao Chen6Weizong Weng7Qirong Zhou8Jin Cui9Liehu Cao10Department of Orthopedics, PLA General Hospital, Beijing, ChinaBasic Medical School, Naval Military Medical University, Shanghai, ChinaDepartment of Emergency, General Hospital of Central Theather Command, Wuhan, ChinaDepartment of Orthopedics, Shanghai Baoshan Luodian Hospital, Shanghai, ChinaDepartment of Orthopedics, Shanghai Baoshan Luodian Hospital, Shanghai, ChinaDepartment of Orthopedics Trauma, Shanghai Changhai Hospital, Naval Military Medical University, Shanghai, ChinaDepartment of Orthopedics Trauma, Shanghai Changhai Hospital, Naval Military Medical University, Shanghai, ChinaDepartment of Orthopedics Trauma, Shanghai Changhai Hospital, Naval Military Medical University, Shanghai, ChinaDepartment of Orthopedics Trauma, Shanghai Changhai Hospital, Naval Military Medical University, Shanghai, ChinaDepartment of Orthopedics Trauma, Shanghai Changhai Hospital, Naval Military Medical University, Shanghai, ChinaDepartment of Orthopedics, Shanghai Baoshan Luodian Hospital, Shanghai, ChinaMyostatin is a crucial cytokine that is widely present in skeletal muscle and that negatively regulates the growth and development of muscle cells. Recent research has shown that myostatin might play an essential role in bone metabolism. In RAW264.7 cells and bone marrow monocytes (BMMCs), myostatin activates the expression of the II type receptor ActR II B. Here, we report that myostatin significantly promoted RANKL/M-CSF-induced osteoclastogenesis and activated NF-κB and MAPK pathways in vitro via the Ccdc50 gene. Overexpression of myostatin promoted osteoclastogenesis and osteoclastogenesis-related markers including c-Src, MMP9, CTR, CK, and NFATc1. Specifically, myostatin increased the phosphorylation of Smad2, which led to the activation of NF-κB and MAPK pathways to activate osteoclastogenesis. Ccdc50 was identified as a gene whose expression was highly decreased in osteoclastogenesis upon myostatin treatment, and it could inhibit the function of myostatin in osteoclastogenesis by blocking NF-κB and MAPKs pathways. Our study indicates that myostatin is a promising candidate target for inhibiting RANKL-mediated osteoclastogenesis and might participate in therapy for osteoporosis, and that the Ccdc50 gene plays a significant role in the regulatory process.https://www.frontiersin.org/articles/10.3389/fphar.2020.565163/fullosteoclastogenesismyostatinCcdc50Receptor activator of NF-κB ligandNF-κB |
| spellingShingle | Xin Zhi Qian Chen Shaojun Song Zhengrong Gu Wenqiang Wei Huiwen Chen Xiao Chen Weizong Weng Qirong Zhou Jin Cui Liehu Cao Myostatin Promotes Osteoclastogenesis by Regulating Ccdc50 Gene Expression and RANKL-Induced NF-κB and MAPK Pathways Frontiers in Pharmacology osteoclastogenesis myostatin Ccdc50 Receptor activator of NF-κB ligand NF-κB |
| title | Myostatin Promotes Osteoclastogenesis by Regulating Ccdc50 Gene Expression and RANKL-Induced NF-κB and MAPK Pathways |
| title_full | Myostatin Promotes Osteoclastogenesis by Regulating Ccdc50 Gene Expression and RANKL-Induced NF-κB and MAPK Pathways |
| title_fullStr | Myostatin Promotes Osteoclastogenesis by Regulating Ccdc50 Gene Expression and RANKL-Induced NF-κB and MAPK Pathways |
| title_full_unstemmed | Myostatin Promotes Osteoclastogenesis by Regulating Ccdc50 Gene Expression and RANKL-Induced NF-κB and MAPK Pathways |
| title_short | Myostatin Promotes Osteoclastogenesis by Regulating Ccdc50 Gene Expression and RANKL-Induced NF-κB and MAPK Pathways |
| title_sort | myostatin promotes osteoclastogenesis by regulating ccdc50 gene expression and rankl induced nf κb and mapk pathways |
| topic | osteoclastogenesis myostatin Ccdc50 Receptor activator of NF-κB ligand NF-κB |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2020.565163/full |
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