Osteosarcoma (OS) is the most common primary malignant bone tumor in children and adolescents, with a high metastatic potential. Despite dramatic changes in OS treatments over the past decades, their efficiency still remains limited, with severe complications and adverse side effects. Key mechanisms underlining tumorigenesis, metastasis and chemotherapy resistance are currently lacking, in turn hindering any progress with respect to developing effective and safe therapeutic strategies against OS. Recently, ADAMTS7, a member of the disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) family, was shown to be involved in osteogenic differentiation‐related pathological processes. ADAMTS7 promotes vascular calcification via disturbing the balance between osteogenic bone morphogenetic protein (BMP)2 (regulating osteogenic differentiation and bone formation during development) and its natural inhibitor cartilage oligomeric matrix protein (Comp). Hence, in the present study, we aimed to investigate the role of ADAMTS7 in the pathological process of OS. We first revealed that ADAMTS7 was decreased in OS tissues. Lower expression of ADAMTS7 was correlated with poor histological differentiation and an advanced clinical stage of OS. Through loss‐ and gain‐function analysis, we further revealed that ADAMTS7 attenuated cell proliferation, migration and invasion, at the same time as promoting the expression of osteogenic differentiation markers in two OS cell lines: MG63 and SAOS2. Moreover, Comp was responsible for the effects of ADAMTS7 on OS pathogenesis by reinforcing cell osteogenic differentiation mediated by BMP2 in vitro. In conclusion, ADAMTS7‐mediated degradation of Comp may provide a potential therapeutic target for the treatment of OS.

中文翻译：

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ADAMTS7 降解 Comp 以促进 BMP2 依赖性成骨分化并改善骨肉瘤的致癌潜力。

骨肉瘤（OS）是儿童和青少年最常见的原发性恶性骨肿瘤，具有很高的转移潜能。尽管过去几十年 OS 治疗发生了巨大变化，但它们的效率仍然有限，具有严重的并发症和不良副作用。目前缺乏强调肿瘤发生、转移和化疗耐药性的关键机制，这反过来阻碍了在开发针对 OS 的有效和安全治疗策略方面的任何进展。最近，具有血小板反应蛋白基序的去整合素和金属蛋白酶 (ADAMTS) 家族成员 ADAMTS7 被证明参与成骨分化相关的病理过程。ADAMTS7 通过扰乱成骨性骨形态发生蛋白 (BMP)2（在发育过程中调节成骨分化和骨形成）与其天然抑制剂软骨寡聚基质蛋白 (Comp) 之间的平衡来促进血管钙化。因此，在本研究中，我们旨在研究 ADAMTS7 在 OS 病理过程中的作用。我们首先揭示了 ADAMTS7 在 OS 组织中减少。ADAMTS7 的低表达与组织学分化差和 OS 的晚期临床阶段相关。通过损失函数和增益函数分析，我们进一步发现 ADAMTS7 减弱细胞增殖、迁移和侵袭，同时促进两种 OS 细胞系：MG63 和 SAOS2 中成骨分化标志物的表达。而且，体外。总之，ADAMTS7 介导的 Comp 降解可能为 OS 的治疗提供潜在的治疗靶点。