Research Papers: Gerotarget (Focus on Aging):
HIF-1α:CRAT:miR-144-3p axis dysregulation promotes osteoarthritis chondrocyte apoptosis and VLCFA accumulation
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Abstract
Jinsoo Song1,*, Yeon-Ho Kang1,*, Sik Yoon2, Churl-Hong Chun3 and Eun-Jung Jin1
1 Department of Biological Sciences, College of Natural Sciences, Wonkwang University, Iksan, Chunbuk, Korea
2 Department of Anatomy, Pusan National University School of Medicine, Yangsan, Korea
3 Department of Orthopedic Surgery, Wonkwang University School of Medicine, Iksan, Chunbuk, Korea
* These authors hve contributed equally to this work
Correspondence to:
Eun-Jung Jin, email:
Keywords: osteoarthritis, very-long-chain fatty acid, CRAT, miR-144-3p, HIF-1α, Gerotarget
Received: May 16, 2017 Accepted: August 14, 2017 Published: September 01, 2017
Abstract
The functional role(s) of peroxisomes in osteoarthritis remains unclear. We demonstrated that peroxisomal dysfunction in osteoarthritis is responsible for very-long-chain fatty acid (VLCFA) accumulation. Through gene-profiling analyses, we identified CRAT as the gene responsible for this event. CRAT expression was suppressed in osteoarthritis chondrocytes, and its knockdown yielded pathological osteoarthritic characteristics, including VLCFA accumulation, apoptosis, autophagic inhibition, and mitochondrial dysfunction. Subsequent miRNA profiling revealed that peroxisomal dysfunction upregulates miR-144-3p, which overlapped with the osteoarthritis pathological characteristics observed upon CRAT knockdown. Moreover, knocking down HIF-1α in normal chondrocytes suppressed CRAT expression while stimulating miR-144-3p. Our data indicate that deregulation of a HIF-1a:CRAT:miR-144-3p axis impairs peroxisomal function during the pathogenesis of osteoarthritis.
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PII: 20615