%0 Journal Article
%T Evidence that miRİ\146a attenuates agingİ\ and traumaİ\induced osteoarthritis by inhibiting Notch1, ILİ\6, and ILİ\1 mediated catabolism
%A Jing Ding
%A Jing Li
%A Kun Yang
%A Shaohua Du
%A Xu Yang
%A Ying Zhang
%A Yingİ\Jie Guan
%A Yun Gao
%J Archive of "Aging Cell".
%D 2018
%R 10.1111/acel.12752
%X Primary osteoarthritis (OA) is associated with aging, while postİ\traumatic OA (PTOA) is associated with mechanical injury and inflammation. It is not clear whether the two types of osteoarthritis share common mechanisms. We found that miRİ\146a, a microRNAİ\associated with inflammation, is activated by cyclic load in the physiological range but suppressed by mechanical overload in human articular chondrocytes. Furthermore, miRİ\146a expression is decreased in the OA lesions of human articular cartilage. To understand the role of miRİ\146a in osteoarthritis, we systemically characterized mice in which miRİ\146a is either deficient in whole body or overexpressed in chondrogenic cells specifically. miRİ\146aİ\deficient mice develop early onset of OA characterized by cartilage degeneration, synovitis, and osteophytes. Conversely, miRİ\146a chondrogenic overexpressing mice are resistant to agingİ\associated OA. Loss of miRİ\146a exacerbates articular cartilage degeneration during PTOA, while chondrogenic overexpression of miRİ\146a inhibits PTOA. Thus, miRİ\146a inhibits both OA and PTOA in mice, suggesting a common protective mechanism initiated by miRİ\146a. miRİ\146a suppresses ILİ\1ĤÂ of catabolic factors, and we provide evidence that miRİ\146a directly inhibits Notch1 expression. Therefore, such inhibition of Notch1 may explain suppression of inflammatory mediators by miRİ\146a. Chondrogenic overexpression of miRİ\146a or intraİ\articular administration of a Notch1 inhibitor alleviates ILİ\1ĤÂİ\induced catabolism and rescues joint degeneration in miRİ\146aİ\deficient mice, suggesting that miRİ\146a is sufficient to protect OA pathogenesis by inhibiting Notch signaling in the joint. Thus, miRİ\146a may be used to counter both agingİ\associated OA and mechanical injuryİ\/inflammationİ\induced PTOA
%K aging
%K cartilage
%K inflammation
%K miRİ\146a
%K Notch1
%K osteoarthritis
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5946074/