Phytic acid/magnesium ion complex coating on PEEK fiber woven fabric as an artificial ligament with anti-fibrogenesis and osteogenesis for ligament-bone healing.

Development of an artificial ligament possessing osteogenic activity to enhance ligament-bone healing for reconstruction of anterior cruciate ligament (ACL) is a great challenge. Herein, polyetheretherketone fibers (PKF) were coated with phytic acid (PA)/magnesium (Mg) ions complex (PKPM), which were woven into fabrics as an artificial ligament. The results demonstrated that PKPM with PA/Mg complex coating exhibited optimized surface properties with improved hydrophilicity and surface energy, and slow release of Mg ions. PKPM significantly enhanced responses of rat bone marrow stem cells in vitro. Moreover, PKPM remarkably promoted M2 macrophage polarization that upregulated production of anti-inflammatory cytokine while inhibited M1 macrophage polarization that downregulated production of pro-inflammatory cytokine in vitro. Further, PKPM inhibited fibrous encapsulation by preventing M1 macrophage polarization while promoted osteogenesis for ligament-bone healing by triggering M2 macrophage polarization in vivo. The results suggested that the downregulation of M1 macrophage polarization for inhibiting fibrogenesis and upregulation of M2 macrophage polarization for improving osteogenesis of PKPM were attributed to synergistic effects of PA and sustained release of Mg ions. In summary, PKPM with PA/Mg complex coating upregulated pro-osteogenic macrophage polarization that supplied a profitable anti-inflammatory environments for osteogenesis and ligament-bone healing, thereby possessing tremendous potential for reconstruction of ACL.

Hydrostatic pressure induces osteogenic differentiation of adipose-derived mesenchymal stem cells through increasing lncRNA-PAGBC.

Induced osteogenesis of adipose-derived mesenchymal stem cells (AMSCs) has been used to facilitate bone regeneration. Specifically, hydrostatic pressure (HP) has been implicated as a key regulator of AMSC differentiation, whereas the mechanisms that underlie the effects of HP on osteogenesis of AMSCs are not fully understood. Long noncoding RNAs (lncRNAs) are emerging regulators for osteogenic differentiation from AMSCs. In the current study, we found that lncRNA-PAGBC was a specific lncRNA that significantly upregulated during osteogenic differentiation of AMSCs based on published database. HP increased lncRNA-PAGBC, which is a competitive endogenous RNA (ceRNA) that binds to the osteogenesis-inhibitory microRNA, miR-133b, to regulate osteogenic differentiation of AMSCs. Moreover, a key osteogenesis-trigger gene, runt-related transcription factor 2 (RUNX2), was identified as a target gene for miR-133b. Suppression of RUNX2 by miR-133b caused impaired osteogenic differentiation of AMSCs. Furthermore, lncRNA-PAGBC overexpression upregulated, whereas lncRNA-PAGBC silencing decreased the expression of RUNX2 through miR-133b. Together, these data suggest that HP induces osteogenic differentiation of AMSCs through increasing lncRNA-PAGBC.