miR-122 Exerts Inhibitory Effects on Osteoblast Proliferation/Differentiation in Osteoporosis by Activating the PCP4-Mediated JNK Pathway
Osteoporosis is characterized by the reduction of bone mineral density and deterioration of bone quality which leads to high risk of fractures. Some microRNAs (miRNAs) have been confirmed as potential modulators of osteoblast differentiation to maintain bone mass maintenance. We aimed to clarify whe...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-06-01
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| Series: | Molecular Therapy: Nucleic Acids |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253120300159 |
| _version_ | 1819064583057309696 |
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| author | Yi-Chen Meng Tao Lin Heng Jiang Zheng Zhang Lun Shu Jia Yin Xiao Ma Ce Wang Rui Gao Xu-Hui Zhou |
| author_facet | Yi-Chen Meng Tao Lin Heng Jiang Zheng Zhang Lun Shu Jia Yin Xiao Ma Ce Wang Rui Gao Xu-Hui Zhou |
| author_sort | Yi-Chen Meng |
| collection | DOAJ |
| description | Osteoporosis is characterized by the reduction of bone mineral density and deterioration of bone quality which leads to high risk of fractures. Some microRNAs (miRNAs) have been confirmed as potential modulators of osteoblast differentiation to maintain bone mass maintenance. We aimed to clarify whether miR-122 could regulate osteoblast differentiation in ovariectomized rats with osteoporosis. miR-122 was upregulated and Purkinje cell protein 4 (PCP4) was downregulated in ovariectomized rats. PCP4 was identified as a target of miR-122 by dual-luciferase reporter gene assay. We transfected isolated osteoblasts from ovariectomized rats with miR-122 mimic or inhibitor or PCP4 overexpression vectors. Proliferation and differentiation of osteoblasts were repressed by the overexpression of miR-122 but enhanced by overexpression of PCP4. miR-122 could induce the activation of the c-Jun NH2-terminal kinase (JNK) signaling pathway, while PCP4 blocked this pathway. Rescue experiments further demonstrated that the inhibiting effects of miR-122 on osteoblast differentiation could be compensated by activation of the PCP4 or inhibition of JNK signaling pathway. Collectively, our data imply that miR-122 inhibits osteoblast proliferation and differentiation in rats with osteoporosis, highlighting a novel therapeutic target for osteoporotic patients. |
| first_indexed | 2024-12-21T15:32:52Z |
| format | Article |
| id | doaj.art-c0d5e6c1ff224af1ad0e3541752eb1e5 |
| institution | Directory Open Access Journal |
| issn | 2162-2531 |
| language | English |
| last_indexed | 2024-12-21T15:32:52Z |
| publishDate | 2020-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj.art-c0d5e6c1ff224af1ad0e3541752eb1e52022-12-21T18:58:43ZengElsevierMolecular Therapy: Nucleic Acids2162-25312020-06-0120345358miR-122 Exerts Inhibitory Effects on Osteoblast Proliferation/Differentiation in Osteoporosis by Activating the PCP4-Mediated JNK PathwayYi-Chen Meng0Tao Lin1Heng Jiang2Zheng Zhang3Lun Shu4Jia Yin5Xiao Ma6Ce Wang7Rui Gao8Xu-Hui Zhou9Department of Orthopedics, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. ChinaDepartment of Orthopedics, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. ChinaDepartment of Orthopedics, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. ChinaDepartment of Orthopedics, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. ChinaDepartment of Orthopedics, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. ChinaDepartment of Orthopedics, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. ChinaDepartment of Orthopedics, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. ChinaDepartment of Orthopedics, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. ChinaDepartment of Orthopedics, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. ChinaDepartment of Orthopedics, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China; Corresponding author: Xu-Hui Zhou, PhD, Department of Orthopedics, Changzheng Hospital, Second Military Medical University, No. 415, Fengyang Road, Shanghai 200003, P.R. China.Osteoporosis is characterized by the reduction of bone mineral density and deterioration of bone quality which leads to high risk of fractures. Some microRNAs (miRNAs) have been confirmed as potential modulators of osteoblast differentiation to maintain bone mass maintenance. We aimed to clarify whether miR-122 could regulate osteoblast differentiation in ovariectomized rats with osteoporosis. miR-122 was upregulated and Purkinje cell protein 4 (PCP4) was downregulated in ovariectomized rats. PCP4 was identified as a target of miR-122 by dual-luciferase reporter gene assay. We transfected isolated osteoblasts from ovariectomized rats with miR-122 mimic or inhibitor or PCP4 overexpression vectors. Proliferation and differentiation of osteoblasts were repressed by the overexpression of miR-122 but enhanced by overexpression of PCP4. miR-122 could induce the activation of the c-Jun NH2-terminal kinase (JNK) signaling pathway, while PCP4 blocked this pathway. Rescue experiments further demonstrated that the inhibiting effects of miR-122 on osteoblast differentiation could be compensated by activation of the PCP4 or inhibition of JNK signaling pathway. Collectively, our data imply that miR-122 inhibits osteoblast proliferation and differentiation in rats with osteoporosis, highlighting a novel therapeutic target for osteoporotic patients.http://www.sciencedirect.com/science/article/pii/S2162253120300159osteoporosismicroRNA-122PCP4JNK signaling pathwayosteoblastsproliferation |
| spellingShingle | Yi-Chen Meng Tao Lin Heng Jiang Zheng Zhang Lun Shu Jia Yin Xiao Ma Ce Wang Rui Gao Xu-Hui Zhou miR-122 Exerts Inhibitory Effects on Osteoblast Proliferation/Differentiation in Osteoporosis by Activating the PCP4-Mediated JNK Pathway Molecular Therapy: Nucleic Acids osteoporosis microRNA-122 PCP4 JNK signaling pathway osteoblasts proliferation |
| title | miR-122 Exerts Inhibitory Effects on Osteoblast Proliferation/Differentiation in Osteoporosis by Activating the PCP4-Mediated JNK Pathway |
| title_full | miR-122 Exerts Inhibitory Effects on Osteoblast Proliferation/Differentiation in Osteoporosis by Activating the PCP4-Mediated JNK Pathway |
| title_fullStr | miR-122 Exerts Inhibitory Effects on Osteoblast Proliferation/Differentiation in Osteoporosis by Activating the PCP4-Mediated JNK Pathway |
| title_full_unstemmed | miR-122 Exerts Inhibitory Effects on Osteoblast Proliferation/Differentiation in Osteoporosis by Activating the PCP4-Mediated JNK Pathway |
| title_short | miR-122 Exerts Inhibitory Effects on Osteoblast Proliferation/Differentiation in Osteoporosis by Activating the PCP4-Mediated JNK Pathway |
| title_sort | mir 122 exerts inhibitory effects on osteoblast proliferation differentiation in osteoporosis by activating the pcp4 mediated jnk pathway |
| topic | osteoporosis microRNA-122 PCP4 JNK signaling pathway osteoblasts proliferation |
| url | http://www.sciencedirect.com/science/article/pii/S2162253120300159 |
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