Abstract
Objectives: Osteoclast differentiation is regulated by transcriptional, post-transcriptional and post-translational mechanisms. Micro-ribonucleic acids (miRNAs) are 20–24 nucleotides long non-coding RNAs involved in post-translational regulation of gene expressions during osteoclast differentiation. The objective of the present study was to investigate the role played by the miRNA, miR-338-3p, in osteoclastogenesis. Methods: Osteoclastogenesis was induced in murine RAW264.7 cells using M-CSF and RANKL. The differentiated cells were harvested at designated times for TRAP staining and detection of designated gene expressions. A synthetic miR-338-3p mimic or its inhibitor was transfected into RAW264.7 cells prior to the induction of osteoclastogenesis. The effects of mimic or inhibitor on osteoclastogenesis were examined by qRT-PCR and TRAP staining. Bioinformatic analysis and luciferase activity were performed to identify the relationship between miR-338-3p and the transcription factor MafB. The miR-338-3p mimic and MafB siRNA were co-transfected into RAW264.7 cells to evaluate the cross-talk between miR-338-3p and MafB. Results: miR-338-3p was increased significantly during osteoclast differentiation. Overexpression of miR-338-3p promoted osteoclastogenesis while its inhibition had the opposite effect. Bioinformatic analysis and dual luciferase assays indicated that miR-338-3p targeted MafB to repress its gene expression. MafB knockdown by RNA silencing blocked the promotional effect of miR-338-3p on osteoclast differentiation. Conclusion: Because miR-338-3p is crucial for osteoclastic differentiation via targeting of the transcription factor MafB, inhibition of this miRNA represents a potential strategy for modulating osteoporosis in an aging population. Clinical significance: Understanding the role played by miR-338-3p in osteoclast differentiation bridges the gap between the pathogenesis of osteoporosis and the quest for novel therapeutics to reduce the risk of bone fracture associated with this global disease.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 91-97 |
| Number of pages | 7 |
| Journal | Journal of Dentistry |
| Volume | 82 |
| DOIs | |
| State | Published - Mar 2019 |
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Keywords
- Osteoclasts
- Osteoporosis
- Transcription factor MafB
- Transfection
- microRNA
ASJC Scopus subject areas
- Dentistry(all)
Cite this
A potential therapeutic target for regulating osteoporosis via suppression of osteoclast differentiation. / Sun, Qin; Zhang, Boran; Zhu, Wei; Wei, Wei; Ma, Jingzhi; Tay, Franklin Chi Meng.
In: Journal of Dentistry, Vol. 82, 03.2019, p. 91-97.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A potential therapeutic target for regulating osteoporosis via suppression of osteoclast differentiation
AU - Sun, Qin
AU - Zhang, Boran
AU - Zhu, Wei
AU - Wei, Wei
AU - Ma, Jingzhi
AU - Tay, Franklin Chi Meng
PY - 2019/3
Y1 - 2019/3
N2 - Objectives: Osteoclast differentiation is regulated by transcriptional, post-transcriptional and post-translational mechanisms. Micro-ribonucleic acids (miRNAs) are 20–24 nucleotides long non-coding RNAs involved in post-translational regulation of gene expressions during osteoclast differentiation. The objective of the present study was to investigate the role played by the miRNA, miR-338-3p, in osteoclastogenesis. Methods: Osteoclastogenesis was induced in murine RAW264.7 cells using M-CSF and RANKL. The differentiated cells were harvested at designated times for TRAP staining and detection of designated gene expressions. A synthetic miR-338-3p mimic or its inhibitor was transfected into RAW264.7 cells prior to the induction of osteoclastogenesis. The effects of mimic or inhibitor on osteoclastogenesis were examined by qRT-PCR and TRAP staining. Bioinformatic analysis and luciferase activity were performed to identify the relationship between miR-338-3p and the transcription factor MafB. The miR-338-3p mimic and MafB siRNA were co-transfected into RAW264.7 cells to evaluate the cross-talk between miR-338-3p and MafB. Results: miR-338-3p was increased significantly during osteoclast differentiation. Overexpression of miR-338-3p promoted osteoclastogenesis while its inhibition had the opposite effect. Bioinformatic analysis and dual luciferase assays indicated that miR-338-3p targeted MafB to repress its gene expression. MafB knockdown by RNA silencing blocked the promotional effect of miR-338-3p on osteoclast differentiation. Conclusion: Because miR-338-3p is crucial for osteoclastic differentiation via targeting of the transcription factor MafB, inhibition of this miRNA represents a potential strategy for modulating osteoporosis in an aging population. Clinical significance: Understanding the role played by miR-338-3p in osteoclast differentiation bridges the gap between the pathogenesis of osteoporosis and the quest for novel therapeutics to reduce the risk of bone fracture associated with this global disease.
AB - Objectives: Osteoclast differentiation is regulated by transcriptional, post-transcriptional and post-translational mechanisms. Micro-ribonucleic acids (miRNAs) are 20–24 nucleotides long non-coding RNAs involved in post-translational regulation of gene expressions during osteoclast differentiation. The objective of the present study was to investigate the role played by the miRNA, miR-338-3p, in osteoclastogenesis. Methods: Osteoclastogenesis was induced in murine RAW264.7 cells using M-CSF and RANKL. The differentiated cells were harvested at designated times for TRAP staining and detection of designated gene expressions. A synthetic miR-338-3p mimic or its inhibitor was transfected into RAW264.7 cells prior to the induction of osteoclastogenesis. The effects of mimic or inhibitor on osteoclastogenesis were examined by qRT-PCR and TRAP staining. Bioinformatic analysis and luciferase activity were performed to identify the relationship between miR-338-3p and the transcription factor MafB. The miR-338-3p mimic and MafB siRNA were co-transfected into RAW264.7 cells to evaluate the cross-talk between miR-338-3p and MafB. Results: miR-338-3p was increased significantly during osteoclast differentiation. Overexpression of miR-338-3p promoted osteoclastogenesis while its inhibition had the opposite effect. Bioinformatic analysis and dual luciferase assays indicated that miR-338-3p targeted MafB to repress its gene expression. MafB knockdown by RNA silencing blocked the promotional effect of miR-338-3p on osteoclast differentiation. Conclusion: Because miR-338-3p is crucial for osteoclastic differentiation via targeting of the transcription factor MafB, inhibition of this miRNA represents a potential strategy for modulating osteoporosis in an aging population. Clinical significance: Understanding the role played by miR-338-3p in osteoclast differentiation bridges the gap between the pathogenesis of osteoporosis and the quest for novel therapeutics to reduce the risk of bone fracture associated with this global disease.
KW - Osteoclasts
KW - Osteoporosis
KW - Transcription factor MafB
KW - Transfection
KW - microRNA
UR - http://www.scopus.com/inward/record.url?scp=85061080454&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85061080454&partnerID=8YFLogxK
U2 - 10.1016/j.jdent.2019.01.015
DO - 10.1016/j.jdent.2019.01.015
M3 - Article
C2 - 30716449
AN - SCOPUS:85061080454
VL - 82
SP - 91
EP - 97
JO - Journal of Dentistry
JF - Journal of Dentistry
SN - 0300-5712
ER -