Inhibition of osteoclastogenesis by stem cell-derived extracellular matrix through modulation of intracellular reactive oxygen species

Abstract

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.

Keywords: Bone marrow monocytes; Extracellular matrix; NF-κB; Osteoclasts; Reactive oxygen species.