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Tytuł pozycji:

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

Tytuł:
Chondroprotective Effects of a Histone Deacetylase Inhibitor, Panobinostat, on Pain Behavior and Cartilage Degradation in Anterior Cruciate Ligament Transection-Induced Experimental Osteoarthritic Rats.
Autorzy:
Wen ZH; Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung 80424, Taiwan.
Huang JS; Section of Orthopedics, Department of Surgery, Antai Medical Care Corporation Anti Tian-Sheng Memorial Hospital, PingTong 92842, Taiwan.
Lin YY; Department of Sports Medicine, China Medical University, No. 91 Hsueh-Shih Road, Taichung 40402, Taiwan.
Yao ZK; Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung 80424, Taiwan.; Department of Orthopedics, Kaohsiung Veterans General Hospital, Kaohsiung 81341, Taiwan.
Lai YC; Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung 80424, Taiwan.; Department of Orthopedics, Asia University Hospital, Taichung 41354, Taiwan.
Chen WF; Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung 80424, Taiwan.; Department of Neurosurgery, College of Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, Kaohsiung 83301, Taiwan.
Liu HT; Department of Medical Research, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 97002, Taiwan.
Lin SC; Department of Orthopedic Surgery, Pingtung Christian Hospital, No. 60 Dalian Road, Pingtung 90059, Taiwan.
Tsai YC; National Museum of Marine Biology and Aquarium, Pingtung 94450, Taiwan.
Tsai TC; Section of Nephrology, Department of Medicine, Antai Medical Care Corporation Anti Tian-Sheng Memorial Hospital, Pingtung 92842, Taiwan.
Jean YH; Section of Orthopedics, Department of Surgery, Antai Medical Care Corporation Anti Tian-Sheng Memorial Hospital, PingTong 92842, Taiwan.
Źródło:
International journal of molecular sciences [Int J Mol Sci] 2021 Jul 07; Vol. 22 (14). Date of Electronic Publication: 2021 Jul 07.
Typ publikacji:
Journal Article
Język:
English
Imprint Name(s):
Original Publication: Basel, Switzerland : MDPI, [2000-
MeSH Terms:
Anterior Cruciate Ligament/*drug effects
Cartilage, Articular/*drug effects
Chondrocytes/*drug effects
Histone Deacetylase Inhibitors/*pharmacology
Osteoarthritis, Knee/*drug therapy
Pain/*drug therapy
Panobinostat/*pharmacology
Animals ; Anterior Cruciate Ligament/metabolism ; Anterior Cruciate Ligament Injuries/drug therapy ; Anterior Cruciate Ligament Injuries/metabolism ; Cartilage Diseases/drug therapy ; Cartilage Diseases/metabolism ; Cartilage, Articular/metabolism ; Chondrocytes/metabolism ; Disease Models, Animal ; Male ; Osteoarthritis, Knee/metabolism ; Pain/metabolism ; Rats ; Rats, Wistar ; Weight-Bearing
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Contributed Indexing:
Keywords: histone deacetylases; nociception; osteoarthritis; panobinostat
Substance Nomenclature:
0 (Histone Deacetylase Inhibitors)
9647FM7Y3Z (Panobinostat)
Entry Date(s):
Date Created: 20210724 Date Completed: 20210803 Latest Revision: 20210803
Update Code:
20240105
PubMed Central ID:
PMC8306086
DOI:
10.3390/ijms22147290
PMID:
34298911
Czasopismo naukowe
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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