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Abstract：
Intravenous administration of conditioned medium from stem cells of human exfoliated deciduous teeth (SHED-CM) regenerates mechanically injured osteochondral tissues in mouse temporomandibular joint osteoarthritis (TMJOA). However, the underlying therapeutic mechanisms remain unclear. Here, we showed that SHED-CM alleviated injured TMJ by inducing anti-inflammatory M2 macrophages in the synovium. Depletion of M2 by Mannosylated Clodrosome abolished the osteochondral repair activities of SHED-CM. Administration of CM from M2-induced by SHED-CM (M2-CM) effectively ameliorated mouse TMJOA by inhibiting chondrocyte inflammation and matrix degradation while enhancing chondrocyte proliferation and matrix formation. Notably, in vitro, M2-CM directly suppressed the catabolic activities while enhancing the anabolic activities of interleukin-1β-stimulated mouse primary chondrocytes. M2-CM also inhibited receptor activator of nuclear factor NF-κB ligand-induced osteoclastogenesis in RAW264.7 cells. Secretome analysis of M2-CM and M0-CM revealed that 5 proteins related to anti-inflammation and/or osteochondrogenesis were enriched in M2-CM. Of these proteins, the Wnt signal antagonist, secreted frizzled-related protein 1 (sFRP1), was the most abundant and played an essential role in the shift to anabolic chondrocytes, suggesting that M2 ameliorated TMJOA partly through sFRP1. This study suggests that secretome from SHED exerted remarkable osteochondral regeneration activities in TMJOA through the induction of sFRP1-expressing tissue-repair M2 macrophages.
摘要：
静脉内施用来自人脱落的乳牙干细胞（SHED-CM）的条件培养基可在小鼠颞下颌关节骨关节炎（TMJOA）中再生机械损伤的骨软骨组织。然而,潜在的治疗机制仍不清楚.这里,我们发现SHED-CM通过诱导滑膜中的抗炎M2巨噬细胞减轻了TMJ的损伤。甘露糖基化的Clodrosome对M2的消耗消除了SHED-CM的骨软骨修复活性。施用由SHED-CM诱导的M2(M2-CM)通过抑制软骨细胞炎症和基质降解,同时增强软骨细胞增殖和基质形成,有效改善小鼠TMJOA。值得注意的是,在体外，M2-CM直接抑制分解代谢活性，同时增强白细胞介素-1β刺激的小鼠原代软骨细胞的合成代谢活性。M2-CM还抑制RAW264.7细胞中核因子NF-κB受体激活剂配体诱导的破骨细胞生成。对M2-CM和M0-CM的分泌组分析显示，M2-CM中富含与抗炎和/或骨软骨形成相关的5种蛋白质。在这些蛋白质中，Wnt信号拮抗剂，分泌型卷曲相关蛋白1（sFRP1），是最丰富的，在向合成软骨细胞的转变中起着至关重要的作用，表明M2部分通过sFRP1改善TMJOA。这项研究表明，通过诱导表达sFRP1的组织修复M2巨噬细胞，SHED的分泌体在TMJOA中发挥了显着的骨软骨再生活性。
