Decellularized extracellular matrix (ECM) derived from stem cells has been shown as a promising biomaterial for bone regeneration because of the promotion effect on osteogenesis in mesenchymal stem cells (MSCs). However, bone regeneration is also influenced by bone resorption and little is known about the effect of cell-derived ECM on osteoclast differentiation. In this study, ECM was deposited by MSCs and, after decellularization, the effect of ECM on osteoclastogenesis of bone marrow monocytes (BMMs) was investigated in comparison to standard tissue culture polystyrene. Our results showed that cell-derived ECM improved BMM proliferation but potently inhibited osteoclast differentiation, evidenced by down-regulation of multinucleated tartrate-resistant acid phosphatase (TRAP)-positive cells, areas of actin rings, and osteoclast-specific gene expression. ECM-mediated attenuation of intracellular reactive oxygen species (ROS) was suggested to play a rival role in the inhibition of osteoclastogenesis, because exogenous hydrogen peroxide supplementation partially rescued the ECM-inhibited osteoclastogenesis. Furthermore, rather than collagen type I, fibronectin in the ECM contributed to ECM-mediated anti-osteoclastogenesis. In conclusion, stem cell-derived decellularized ECM significantly suppressed osteoclastogenesis via the attenuation of intracellular ROS. The anti-osteoclastogenic property of cell-derived ECM may benefit its clinical use for modulating bone remodeling and promoting bone tissue engineering.

Statement of Significance

Decellularized extracellular matrix (ECM) derived from stem cells has been shown as a promising biomaterial for bone regeneration; however, bone remodeling is influenced by bone resorption and little is known about the effect of cell-derived ECM on osteoclast differentiation. Cell-derived ECM improved BMM proliferation but potently inhibited osteoclast differentiation. ECM-mediated attenuation of intracellular reactive oxygen species was suggested to play a rival role in osteoclastogenesis. Fibronectin in cell-derived ECM also contributed to ECM-mediated anti-osteoclastogenesis. The anti-osteoclastogenic property of cell-derived ECM may benefit clinically for modulating bone remodeling and promoting bone tissue engineering.

由于对间充质干细胞（MSCs）促进成骨作用，源自干细胞的脱细胞细胞外基质（ECM）已被证明是用于骨再生的有前途的生物材料。但是，骨再生也受骨吸收的影响，关于细胞源性ECM对破骨细胞分化的影响知之甚少。在这项研究中，ECM由MSC沉积，并在脱细胞后，与标准组织培养物聚苯乙烯相比，研究了ECM对骨髓单核细胞（BMM）破骨细胞生成的影响。我们的结果表明，细胞衍生的ECM可改善BMM增殖，但有效抑制破骨细胞分化，这由多核抗酒石酸酸性磷酸酶（TRAP）阳性细胞，肌动蛋白环区域，和破骨细胞特异性基因表达。ECM介导的细胞内活性氧物质（ROS）的衰减被认为在破骨细胞形成的抑制中起竞争作用，因为外源性过氧化氢的补充部分挽救了ECM抑制的破骨细胞形成。此外，ECM中的纤连蛋白不是I型胶原，而是促成ECM介导的抗破骨细胞生成。总之，干细胞衍生的脱细胞ECM通过减弱细胞内ROS来显着抑制破骨细胞生成。细胞源性ECM的抗破骨细胞特性可能有益于其临床应用，可用于调节骨重塑和促进骨组织工程。ECM介导的细胞内活性氧物质（ROS）的衰减被认为在破骨细胞形成的抑制中起竞争作用，因为外源性过氧化氢的补充部分挽救了ECM抑制的破骨细胞形成。此外，ECM中的纤连蛋白不是I型胶原，而是促成ECM介导的抗破骨细胞生成。总之，干细胞衍生的脱细胞ECM通过减弱细胞内ROS来显着抑制破骨细胞生成。细胞源性ECM的抗破骨细胞特性可能有益于其临床应用，可用于调节骨重塑和促进骨组织工程。ECM介导的细胞内活性氧物质（ROS）的衰减被认为在破骨细胞形成的抑制中起竞争作用，因为外源性过氧化氢的补充部分挽救了ECM抑制的破骨细胞形成。此外，ECM中的纤连蛋白不是I型胶原，而是促成ECM介导的抗破骨细胞生成。总之，干细胞衍生的脱细胞ECM通过减弱细胞内ROS来显着抑制破骨细胞生成。细胞源性ECM的抗破骨细胞特性可能有益于其临床应用，可用于调节骨重塑和促进骨组织工程。ECM中的纤连蛋白有助于ECM介导的抗破骨细胞生成。总之，干细胞衍生的脱细胞ECM通过减弱细胞内ROS来显着抑制破骨细胞生成。细胞源性ECM的抗破骨细胞特性可能有益于其临床应用，可用于调节骨重塑和促进骨组织工程。ECM中的纤连蛋白有助于ECM介导的抗破骨细胞生成。总之，干细胞衍生的脱细胞ECM通过减弱细胞内ROS来显着抑制破骨细胞生成。细胞源性ECM的抗破骨细胞特性可能有益于其临床应用，可用于调节骨重塑和促进骨组织工程。

重要声明

来自干细胞的脱细胞的细胞外基质（ECM）已被证明是一种有希望的骨再生生物材料。然而，骨重塑受骨吸收的影响，关于细胞源性ECM对破骨细胞分化的影响知之甚少。细胞源性ECM可改善BMM增殖，但有效抑制破骨细胞分化。建议ECM介导的细胞内活性氧物质的衰减在破骨细胞形成中起竞争作用。细胞源性ECM中的纤连蛋白也有助于ECM介导的抗破骨细胞生成。细胞源性ECM的抗破骨细胞作用可能在临床上有益于调节骨重塑和促进骨组织工程。