The Role of HDACs and HDACi in Cartilage and Osteoarthritis

Zhang, He; Ji, Lü; Yang, Yue; Zhang, Xiaoning; Ye, Gang; Bai, Lan

doi:10.3389/fcell.2020.560117

Cited by 31 publications

(18 citation statements)

References 100 publications

(123 reference statements)

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“…Some other HDACi have been trialed and these include orinostat (SAHA), ricolinostat (ACY-1215), givinostat (ITF2357), butyrateacid, and valproicacid (VPA). The results showed that they had chondroprotective effects through inhibition of the expression of MMPs and pro-inflammatory cytokines in human OA chondrocytes via NF-κB and MAPK signaling pathways ( Zhang H. et al, 2020 ).…”

Section: Anti-cellular Senescence Strategiesmentioning

confidence: 99%

Aging, Cell Senescence, the Pathogenesis and Targeted Therapies of Osteoarthritis

Zhang

Liang

et al. 2021

Front. Pharmacol.

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Osteoarthritis (OA) is a chronic, debilitating joint disease characterized by progressive destruction of articular cartilage. For a long time, OA has been considered as a degenerative disease, while recent observations indicate the mechanisms responsible for the pathogenesis of OA are multifaceted. Aging is a key factor in its development. Current treatments are palliative and no disease modifying anti-osteoarthritis drugs (DMOADs) are available. In addition to articular cartilage degradation, cellular senescence, synovial inflammation, and epigenetic alterations may all have a role in its formation. Accumulating data demonstrate a clear relationship between the senescence of articular chondrocytes and OA formation and progression. Inhibition of cell senescence may help identify new agents with the properties of DMOADs. Several anti-cellular senescence strategies have been proposed and these include sirtuin-activating compounds (STACs), senolytics, and senomorphics drugs. These agents may selectively remove senescent cells or ameliorate their harmful effects. The results from preclinical experiments and clinical trials are inspiring. However, more studies are warranted to confirm their efficacy, safety profiles and adverse effects of these agents.

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Section: Anti-cellular Senescence Strategiesmentioning

confidence: 99%

Aging, Cell Senescence, the Pathogenesis and Targeted Therapies of Osteoarthritis

Zhang

Liang

et al. 2021

Front. Pharmacol.

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“…Osteoarthritis (OA) is a common degenerative disorder of the joints that accounts for major physical pain in older adults [ 1 , 2 ]. OA could result in severe joint pain, stiffness, limited motion, disability, and in serious cases, the loss of joint mobility [ 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal stem cell-derived extracellular vesicles prevent the development of osteoarthritis via the circHIPK3/miR-124-3p/MYH9 axis

Liu

et al. 2021

J Nanobiotechnol

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Background Extracellular vesicles (EVs) secreted by mesenchymal stem cells (MSCs) may play a vital role in a variety of biological processes, including cartilage regeneration. However, few studies reported their potential in the development of osteoarthritis (OA) previously. In this study, we explored the biological roles and underlying mechanism of MSCs-EVs in OA. Results Co-culture experiments revealed that MSCs-EVs could promote the expression of collagen type II alpha 1 chain (COL2A1), SRY-box transcription factor 9 (SOX9) and Aggrecan while negatively regulate the expression of chondrocyte hypertrophy markers matrix metallopeptidase 13 (MMP-13) and RUNX family transcription factor 2 (Runx2) in mouse chondrocytes in the OA model. Besides, the results of cell experiments indicated that MSCs-EVs could notably weaken the suppression of chondrocyte proliferation, migration and the promotion of chondrocyte apoptosis via interleukin1β (IL-1β) induction. In addition, MSCs-circHIPK3-EVs (EVs derived from MSCs overexpressing circHIPK3) considerably improved IL-1β-induced chondrocyte injury. Mechanistically, we elucidated that circHIPK3 could directly bind to miR-124-3p and subsequently elevate the expression of the target gene MYH9. Conclusion The findings in our study demonstrated that EVs-circHIPK3 participated in MSCs-EVs-mediated chondrocyte proliferation and migration induction and in chondrocyte apoptosis inhibition via the miR-124-3p/MYH9 axis. This offers a promising novel cell-free therapy for treating OA. Graphic abstract

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“…HDACs, a class of epigenetic factors, epigenetically regulate chromatin structure and transcription factor activity by removing acetyl groups from lysine residues on histones [ 10 , 11 , 12 ]. Recent studies have demonstrated that the abnormal activation and differential expression of HDAC contribute to osteoarthritis (OA) pathogenesis [ 10 , 11 , 12 ] and suggested that inhibiting or augmenting the activity of specific HDACs plays an important role in controlling OA development and progression. However, recent intensive studies have demonstrated that the chondroprotective effects of HDAC inhibition attenuate matrix metalloproteinases (MMPs) and consequently reduce cartilage degradation [ 10 , 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

“…Recent studies have demonstrated that the abnormal activation and differential expression of HDAC contribute to osteoarthritis (OA) pathogenesis [ 10 , 11 , 12 ] and suggested that inhibiting or augmenting the activity of specific HDACs plays an important role in controlling OA development and progression. However, recent intensive studies have demonstrated that the chondroprotective effects of HDAC inhibition attenuate matrix metalloproteinases (MMPs) and consequently reduce cartilage degradation [ 10 , 11 , 12 ]. Thus, HDAC inhibitors might emerge as a promising new class of therapeutic drug for OA in recent years.…”

Section: Introductionmentioning

confidence: 99%

Chondroprotective Effects of a Histone Deacetylase Inhibitor, Panobinostat, on Pain Behavior and Cartilage Degradation in Anterior Cruciate Ligament Transection-Induced Experimental Osteoarthritic Rats

Wen

Huang

Lin

et al. 2021

IJMS

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Osteoarthritis (OA) is the most common articular degenerative disease characterized by chronic pain, joint inflammation, and movement limitations, which are significantly influenced by aberrant epigenetic modifications of numerous OA-susceptible genes. Recent studies revealed that both the abnormal activation and differential expression of histone deacetylases (HDACs) might contribute to OA pathogenesis. In this study, we investigated the chondroprotective effects of a marine-derived HDAC inhibitor, panobinostat, on anterior cruciate ligament transection (ACLT)-induced experimental OA rats. The intra-articular administration of 2 or 10 µg of panobinostat (each group, n = 7) per week from the 6th to 17th week attenuates ACLT-induced nociceptive behaviors, including secondary mechanical allodynia and weight-bearing distribution. Histopathological and microcomputed tomography analysis showed that panobinostat significantly prevents cartilage degeneration after ACLT. Moreover, intra-articular panobinostat exerts hypertrophic effects in the chondrocytes of articular cartilage by regulating the protein expressions of HDAC4, HDAC6, HDAC7, runt-domain transcription factor-2, and matrix metalloproteinase-13. The study indicated that HDACs might have different modulations on the chondrocyte phenotype in the early stages of OA development. These results provide new evidence that panobinostat may be a potential therapeutic drug for OA.

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The Role of HDACs and HDACi in Cartilage and Osteoarthritis

Cited by 31 publications

References 100 publications

Aging, Cell Senescence, the Pathogenesis and Targeted Therapies of Osteoarthritis

Aging, Cell Senescence, the Pathogenesis and Targeted Therapies of Osteoarthritis

Mesenchymal stem cell-derived extracellular vesicles prevent the development of osteoarthritis via the circHIPK3/miR-124-3p/MYH9 axis

Chondroprotective Effects of a Histone Deacetylase Inhibitor, Panobinostat, on Pain Behavior and Cartilage Degradation in Anterior Cruciate Ligament Transection-Induced Experimental Osteoarthritic Rats

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