| First Author | Okada K | Year | 2020 |
| Journal | Sci Rep | Volume | 10 |
| Issue | 1 | Pages | 5425 |
| PubMed ID | 32214220 | Mgi Jnum | J:286980 |
| Mgi Id | MGI:6405106 | Doi | 10.1038/s41598-020-62463-4 |
| Citation | Okada K, et al. (2020) Hypoxia-inducible factor-1 alpha maintains mouse articular cartilage through suppression of NF-kappaB signaling. Sci Rep 10(1):5425 |
| abstractText | HIF-1alpha, an essential transcription factor under hypoxic condition, is indispensable for chondrocytes during skeletal development but its expression and roles in articular chondrocytes are yet to be revealed. We examined HIF-1alpha protein expression and the hypoxic condition during mouse osteoarthritis (OA) development using state of the art hypoxic probes and found that its expression decreased as OA progressed, coinciding with the change in hypoxic conditions in articular cartilage. Gain- and loss-of-function of HIF-1alpha in cell culture experiments showed that HIF-1alpha suppressed catabolic genes such as Mmp13 and Hif2a. We confirmed these anticatabolic effects by measuring glycosaminoglycan release from wild type and conditional knock-out mice femoral heads cultured ex vivo. We went on to surgically induce OA in mice with chondrocyte-specific deletion of Hif1a and found that the development of OA was exacerbated. Increased expression of catabolic factors and activation of NF-kappaB signalling was clearly evident in the knock-out mice. By microarray analysis, C1qtnf3 was identified as a downstream molecule of HIF-1alpha, and experiments showed it exerted anti-catabolic effects through suppression of NF-kappaB. We conclude that HIF-1alpha has an anti-catabolic function in the maintenance of articular cartilage through suppression of NF-kappaB signalling. |
