Osteoarthritis and microRNAs: Do They Provide Novel Insights into the Pathophysiology of This Degenerative Disorder?
Abstract
:1. Introduction
2. Materials and Methods
2.1. Search Strategy and Study Selection
2.2. Inclusion and Exclusion Criteria
2.3. Data Extraction
3. Results
3.1. MiRs Expression in OA Patients
3.2. MiRs Involvement in the Pathogenesis of OA
3.3. Effective Roles of miRs in OA Pathophysiology
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Upregulated miRs | Downregulated miRs |
---|---|
miR-195-5p | miR-335-5p |
miR-9 | miR-146 |
miR-25 | miR-149 |
miR-98 | miR-30 |
miR-27a | miR-337-3p |
miR-34b | miR-140 |
miR-30b | miR-146a |
miR-140 | miR-27a-5p |
miR-23a- 3p | miR-329 |
miR-24-3p | miR-655 |
miR-27a-3p | miR-708-3p |
miR-27b-3p | miR-934 |
miR-29c-3p | miR-101-5p |
miR-34a-5p | miR-20 |
miR-186-5p | miR-27b-3p |
miR-483a-5p | miR-26a-5p |
miR-103 | miR-27a |
miR-146a | miR-107 |
miR-218-5p | miR-222 |
miR-449a | miR-320c |
miR-324-5p | miR-26a |
miR-1236 | miR-26b |
miR-16-5p | miR-93-5p |
miR-29b | miR-377-3p |
miR-455-3p | miR-675-3p |
miR-16 | |
miR-132 | |
miR-33b-3p | |
miR-140-3p | |
miR-671-3p | |
miR-140-5p | |
miR-142-5p | |
miR-197 |
Apoptosis | Induced Effect | Signaling Pathway | Reference No. |
---|---|---|---|
miR-195-5p | mRNA and protein levels of IL-1β, IL-6 and TNF-α were significantly enhanced | mir-195-5p activated the lPS-induced repression of the Wnt/β-catenin signaling pathway and activation of the nuclear factor (NF)-κB signaling pathway in ATDC5 cells | [5] |
miR-335-5p | significantly reduces the expression of inflammatory factors (IL-1β, IL-6, and TNF-α) | significantly enhanced expression levels of the autophagy-related genes encoding the autophagy-related proteins Beclin-1, ATG5, and ATG7 | [6] |
miR-9 | reduces the IL-1β mediated production of TNF-α and reduces basal and IL-1β-induced MMP13 protein release | PXR/RXR activation, G-protein coupled receptor (GPCR) signaling and Wnt/b-catenin signaling | [7] |
miR-145 | miR-145 up-regulation decreases LPS-induced inflammatory injury in ATDC5 cells through SAL | functioned in LPS-induced injury by blocking NF-κB and p38MAPK signaling pathways | [9] |
miR-337-3p | - | miR-337-3p in OA increased PTEN expression and thus PI3K/AKT signaling pathway was blocked by PTEN | [13] |
miR-27b-3p | TNF-αand IL-6 levels repressed by the silencing of PVT1 were significantly enhanced by knockdown of miR-27b-3p in C28/I2 cells treated by IL-1β | miR-27b-3p decreased cell viability that was promoted by the silencing of PVT1 in IL-1β-treated C28/I2 cells, miR-27b-3p abrogated the promoting effect of PVT1 knockdown on autophagy in C28/I2 cells challenged by IL-1β | [20] |
miR-125b | - | miR-125b noticeably alleviated the LPS+pc-THRIL-induced JAK1/STAT3 and NF-κB pathways activation | [23] |
miR-26a-5p | - | - | [24] |
miR-107 | - | miR-107 inhibited the activation of AKT/mTOR and NF-κB pathway | [25] |
miR-218-5p | - | The expression of PIK3C2A, Akt, mTOR and S6 was downregulated, while 24 4EBP1 was upregulated | [26] |
miR-222 | - | - | [27] |
miR-140-5p | miR-140-5p reduced the expression of HMGB1 protein, p-AKT (Ser473) and p-PI3K in IL-1β-induced chondrocytes | inhibited the PI3K/ AKT signaling pathway and suppressed the progression of OA through targeting HMGB1 | [28] |
miR-1236 | - | miR-1236 overexpression promotes OA by inhibiting proliferation and induces apoptosis of chondrocytes, partially through PIK3R3 repression. | [29] |
miR-26b | - | - | [30] |
miR-93-5p | Overexpression of miR-93-5p was found to significantly inhibit IL-1β–induced chondrocyte apoptosis. In general, IL-1β enhances the expression of matrix-degrading enzymes (MMP3 and MMP13), which in turn degrade the ECM | miR-93-5p exerted its actions in chondrocytes partially through suppression of TCF4 expression | [31] |
miR-675-3p | miR-675-3p overexpression inhibited the IL-6 and IL-8 expression that was caused by IL-1b stimulation | miR-675-3p mimic markedly attenuated the increase in the GNG5 expression levels | [32] |
miR-29b | - | - | [33] |
miR-455-3p | miR-455-3p significantly inhibited the viability of CHON-001 cells IL-1β-induced apoptosis of CHON-001 was significantly increased by up-regulation of miR-455-3p | miR-455-3p directly regulated COL2A1 expression through binding its 3′UTR sequence | [34] |
miR-142-5p | miR-142-5p overexpression resulted in significantly decreased levels of IL-1β and TNF-α and increased levels of IL-10 | miR-142-5p overexpression downregulated CXCR4 expression | [35] |
Inflammation | Proliferation |
---|---|
miR-195-5p * | miR-195-5p * |
miR-335-5p * | miR-335-5p * |
miR-9 * | miR-140-5p * |
miR-98 | miR-337-3p * |
mir-146 | miR-26a-5p * |
miR-145 * | miR-103 |
miR-140-5p | miR-20 |
miR-140-3p | miR-218-5p * |
miR-146a | miR-320c |
miR-155 | miR-1236 * |
miR-27b-3p * | miR-26a |
miR-125b * | miR-26b * |
miR-27a | miR-377-3p |
miR-140-5p * | miR-675-3p * |
miR-20 | miR-29b * |
miR-377-3p | miR-197 |
miR-455-3p * | |
miR-142-5p * | |
miR-197 | |
miR-23a-3p | |
miR-24-3p | |
miR-29c-3p | |
miR-186-5p |
Apoptosis (Total) | Inflammation (Total) | Proliferation (Total) | Total miRs in All Processes |
19 | 23 | 16 | 58 |
Only apoptosis | Only inflammation | Only proliferation | Total miRs |
3 | 11 | 3 | 17 |
miRs with Protective Roles in OA | Effective Role | miRs with Destructive Roles in OA | Effective Role |
---|---|---|---|
miR-195-5p | inhibits chondrocyte apoptosis and the inflammatory response | miR-9 | - |
miR-335-5p | significantly increases cell viability and autophagy-related factors, and reduces inflammatory mediators | miR-145 | miR-145 down-regulation increases LPS-induced inflammatory injury |
miR-337-3p | inhibits the apoptosis of OA chondrocytes | miR-140 | - |
miR-140-5p | inhibits inflammation mediators and cartilage degradation and upregulates chondrogenic proteins | miR-30b | promotes cartilage degradation |
miR-146a | reduces the expression levels of inflammatory genes and catabolic proteases in nucleus pulposus | miR-23a-3p | inflammatory stimulus |
miR-27a-5p | - | miR-483-5p | severe cartilage damage, cartilage matrix degeneration, and increased chondrocyte hypertrophy |
miR-20 | inhibits chondrocyte proliferation and autophagy | miR-125b | promotes inflammatory injury |
miR-103 | - | miR-26a-5p | - |
miR-222 | induces osteoblast proliferation and attenuates cardiomyocyte hypertrophy | miR-27a | increases the proliferation, apoptosis and inflammation of chondrocytes |
miR-26a | regulates chondrocytes apoptosis | miR-107 | inhibits cell apoptosis and promotes autophagy in OA chondrocytes |
miR-26b | regulates chondrocytes apoptosis | miR-140-5p | increases cartilage degradation |
miR-93-5p | attenuates chondrocyte apoptosis and cartilage degradation | miR-146a | increases and promotes inflammation |
miR-377-3p | alleviates chondrocyte apoptosis and cartilage degradation | miR-218-5p | promotes cartilage destruction |
miR-16 | - | miR-320c | promotes cartilage destruction |
miR-132 | - | miR-449a | promotes chondrocytes degradation |
miR-33b-3p | - | miR-324-5p | - |
miR-140-3p | protective against OA development via inhibition of inflammation and oxidative stress, enhancement of autophagy | miR-1236 | induces cell apoptosis in chondrocytes, suppresses cell proliferation. |
miR-671-3p | - | miR-16-5p | - |
miR-675-3p | inhibits apoptosis, matrix degradation and inflammation of chondrocytes. | miR-29b | facilitates chondrocyte apoptosis |
miR-142-5p | attenuates chondrocyte apoptosis and cartilage degradation | miR-34a-5p | promotes cartilage damage |
miR-197 | promotes chondrocyte proliferation, increases migration, and inhibits inflammation | miR-27b-3p | promotes cartilage damage |
miR-329 | - | miR-455-3p | enhances chondrocytes apoptosis and inflammation |
miR-655 | - | miR-98 | promotes inflammation |
miR-708-3p | - | miR-140-3p | promotes inflammation |
miR-934 | - | miR-24-3p | promotes inflammation |
miR-146 | negative regulator of immune responses | miR-29c-3p | promotes inflammation |
miR-186-5p | promotes inflammation | ||
miR-155 | - |
MiRs | Regulation (Across Other Studies) | Regulation (Found in Our Review) | Reference |
---|---|---|---|
miR-140 | ↑ | ↑↓ | [66] |
miR-146a | ↑ | ↑↓ | [66] |
miR-26a * | ↓ | ↓ | [66] |
miR-26b * | ↓ | ↓ | [66] |
miR-27a | ↓ | ↑↓ | [66] |
miR-27b | ↓ | ↑↓ | [66] |
miR-9 | ↓ | ↑ | [66] |
mir-140 | ↑ | ↑↓ | [67] |
miR-9 * | ↑ | ↑ | [67] |
miR-26a | ↑ | ↓ | [67] |
miR-146a | ↑ | ↑↓ | [67] |
miR-27a | ↓ | ↑↓ | [67] |
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Stanciugelu, S.I.; Homorogan, C.; Selaru, C.; Patrascu, J.M.; Patrascu, J.M.; Stoica, R.; Nitusca, D.; Marian, C. Osteoarthritis and microRNAs: Do They Provide Novel Insights into the Pathophysiology of This Degenerative Disorder? Life 2022, 12, 1914. https://doi.org/10.3390/life12111914
Stanciugelu SI, Homorogan C, Selaru C, Patrascu JM, Patrascu JM, Stoica R, Nitusca D, Marian C. Osteoarthritis and microRNAs: Do They Provide Novel Insights into the Pathophysiology of This Degenerative Disorder? Life. 2022; 12(11):1914. https://doi.org/10.3390/life12111914
Chicago/Turabian StyleStanciugelu, Stefan Iulian, Claudia Homorogan, Cosmin Selaru, Jenel Marian Patrascu, Jenel Marian Patrascu, Raymond Stoica, Diana Nitusca, and Catalin Marian. 2022. "Osteoarthritis and microRNAs: Do They Provide Novel Insights into the Pathophysiology of This Degenerative Disorder?" Life 12, no. 11: 1914. https://doi.org/10.3390/life12111914