Senescent Tissue-Resident Mesenchymal Stromal Cells Are an Internal Source of Inflammation in Human Osteoarthritic Cartilage.
Senescent Tissue-Resident Mesenchymal Stromal Cells Are an Internal Source of Inflammation in Human Osteoarthritic Cartilage.
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DOI：
10.3389/fcell.2021.725071
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发表时间：
2021
影响因子：
5.5
通讯作者：
Chen Q
中科院分区：
文献类型：
--
作者：
Liu W;Brodsky AS;Feng M;Liu Y;Ding J;Jayasuriya CT;Chen Q
Human osteoarthritic cartilage contains not only chondrocytes (OACs), but also mesenchymal stromal cells (OA-MSCs), whose abundance increases during osteoarthritis (OA). However, it is not clear how OA-MSC contributes to OA pathogenesis. Here, we show that aging OA-MSC plays an important role in cell senescence, fibrosis, and inflammation in cartilage. Protein array analysis indicates that OA-MSC expresses pro-inflammatory senescence associated secretory phenotype (SASP) including IL-1β, IL-6, IL-8, and CXCL1, 5, and 6, which play key roles in OA pathogenesis. OAC is a main recipient of the inflammatory signals by expressing receptors of cytokines. RNAseq analysis indicates that the transition from normal cartilage stromal cells (NCSCs) to OA-MSC during aging results in activation of SASP gene expression. This cell transition process can be recapitulated by a serial passage of primary OAC in cell culture comprising (1) OAC dedifferentiation into NCSC-like cells, and (2) its subsequent senescence into pro-inflammatory OA-MSC. While OAC dedifferentiation is mediated by transcriptional repression of chondrogenic gene expression, OA-MSC senescence is mediated by transcriptional activation of SASP gene expression. We postulate that, through replication-driven OAC dedifferentiation and mesenchymal stromal cell (MSC) senescence, OA-MSC becomes an internal source of sterile inflammation in human cartilage joint.
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影响因子：
4.6
作者：
Fellows CR;Williams R;Davies IR;Gohil K;Baird DM;Fairclough J;Rooney P;Archer CW;Khan IM
通讯作者：
Khan IM
人骨关节炎软骨衍生的基质细胞通过TGF-β侧向信号传导激活关节变性。
DOI：
10.1096/fj.202001448r
发表时间：
2020-12
期刊：
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
影响因子：
--
作者：
Liu W;Feng M;Jayasuriya CT;Peng H;Zhang L;Guan Y;Froehlich JA;Terek RM;Chen Q
通讯作者：
Chen Q
来自定型软骨细胞的人软骨来源的祖细胞，用于有效的软骨修复和再生
影响因子：
6
作者：
Jiang Y;Cai Y;Zhang W;Yin Z;Hu C;Tong T;Lu P;Zhang S;Neculai D;Tuan RS;Ouyang HW
通讯作者：
Ouyang HW
DOI：
10.1146/annurev-pathol-121808-102144
发表时间：
2010
期刊：
Annual review of pathology
影响因子：
--
作者：
Coppé JP;Desprez PY;Krtolica A;Campisi J
通讯作者：
Campisi J
影响因子：
5
作者：
Goldring, M B
通讯作者：
Goldring, M B