Synovial cell cross-talk with cartilage plays a major role in the pathogenesis of osteoarthritis
Synovial cell cross-talk with cartilage plays a major role in the pathogenesis of osteoarthritis
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DOI：
10.1038/s41598-020-67730-y
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发表时间：
2020-07-02
影响因子：
4.6
通讯作者：
Kraus, Virginia B.
中科院分区：
文献类型：
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作者：
Chou, Ching-Heng;Jain, Vaibhav;Kraus, Virginia B.
我们使用单细胞RNA测序这一强大工具，阐明了骨关节炎（世界上最广泛的关节炎）中软骨和滑膜之间的分子串扰。基于10，640个滑膜细胞和26，192个软骨细胞的分析，鉴定了多种细胞类型：来自匹配组织的12种不同的滑膜细胞类型和7种不同的关节软骨细胞表型。完整的软骨中富含稳态和肥大的软骨细胞，而受损的软骨中富含前肥大和前肥大的调节性、修复性和前肥大的软骨细胞。共61种细胞因子和生长因子被预测调节7种软骨细胞表型。基于>1%的细胞的产生，55%的细胞因子由滑膜细胞产生（39%仅限于滑膜细胞并且不由软骨细胞表达），并且证实了它们在骨关节炎滑液中的存在。产生IL-1 β（骨关节炎中的经典致病细胞因子）的滑膜细胞，主要是炎性巨噬细胞和树突状细胞，其特征在于共表达对应于HLA-DQA 1、HLA-DQA 2、OLR 1或TLR 2的表面蛋白。消除这些致病性关节内细胞亚群的策略可能是人类骨关节炎的治疗选择。
We elucidated the molecular cross-talk between cartilage and synovium in osteoarthritis, the most widespread arthritis in the world, using the powerful tool of single-cell RNA-sequencing. Multiple cell types were identified based on profiling of 10,640 synoviocytes and 26,192 chondrocytes: 12 distinct synovial cell types and 7 distinct articular chondrocyte phenotypes from matched tissues. Intact cartilage was enriched for homeostatic and hypertrophic chondrocytes, while damaged cartilage was enriched for prefibro- and fibro-, regulatory, reparative and prehypertrophic chondrocytes. A total of 61 cytokines and growth factors were predicted to regulate the 7 chondrocyte cell phenotypes. Based on production by >1% of cells, 55% of the cytokines were produced by synovial cells (39% exclusive to synoviocytes and not expressed by chondrocytes) and their presence in osteoarthritic synovial fluid confirmed. The synoviocytes producing IL-1beta (a classic pathogenic cytokine in osteoarthritis), mainly inflammatory macrophages and dendritic cells, were characterized by co-expression of surface proteins corresponding to HLA-DQA1, HLA-DQA2, OLR1 or TLR2. Strategies to deplete these pathogenic intra-articular cell subpopulations could be a therapeutic option for human osteoarthritis.