Genetic association analysis of the IGFBP7, ADAMTS3, and IL8 genes as the potential osteoarthritis susceptibility that maps to chromosome 4q

Single cell RNA-seq analysis identifies ferroptotic chondrocyte cluster and reveals TRPV1 as an anti-ferroptotic target in osteoarthritis

“…Based on t-SNE analysis, unbiased clustering of the cells parallelly identified four main clusters according to their gene profiles and canonical markers ( Figure 2 b). Particularly, these cell clusters were: (C0) the homeostatic chondrocytes (HomCs) highly expressing COL2A1 , 27 COL3A1 , 28 HAPLN1 29 and PRG4 ; 30 (C1) the stressed chondrocytes (StrCs) preferentially expressing CDKN1A , 31 DNAJB6 , 32 SLC3A2 33 and HSPB1 ; 34 (C2) the regulatory chondrocytes (RegCs) specifically expressing CHI3L1 , 35 CHI3L2 , 35 NBL1 36 and TNC ; 37 and (C3) the degenerative chondrocytes (DegCs) with high expression of COL10A1 , 27 MT1X , 38 IGFB7 , 39 and RAMP1 40 ( Figure 2 c, d). We noticed that, in damaged cartilage, the frequency of HomCs was declined, while StrCs and RegCs were increased ( Figure 2 e), indicating loss of cartilage homeostasis and increased cellular stress in the damaged area than the intact area.…”

Quantitative proteomics reveals regulatory differences in the chondrocyte secretome from human medial and lateral femoral condyles in osteoarthritic patients

“…FSTL1 has been demonstrated to be correlated to the severity of OA disease as well as CHI3L1 [ 43 - 45 ]. SPARC and B2M are correlated to OA while the IGFBP7 has not been correlated to OA previously [ 30 , 39 , 46 ]. IGFBP4 is suggested to inhibit the canonical Wnt signaling pathway, which makes elevated levels of IGFBP4 on the medial side in the LM scored specimen an interesting finding as stimulated Wnt signaling is known to be involved in OA pathogenesis [ 47 - 50 ].…”

Identification of quantitative trait loci for osteoarthritis of hip joints in dogs

“…The contribution of genetic factors to susceptibility to OA is increasingly recognized. Various studies in humans (eg, epidemiologic, twin-pair, and sibling-risk studies), including genome-wide-scanning 7,8 and candidate-gene 9,10 studies, have provided evidence of an important genetic component in the development of OA in human hip joints. The probability of genetic influence on the development of OA in hip and knee joints in humans was estimated to be as high as 65% in a twin study.…”