Anti-MMP2 monoclonal antibody, clone 7F4G9

In this study, the chemokine substance P (SP) was inserted into multilayered systems on titanium (Ti)-based substrates for endogenous mesenchymal stem cell (MSC) recruitment to facilitate bone healing. The multilayer was constructed with cationic chitosan (Chi), SP and anionic gelatin (Gel) via a spin-coater-assisted layer-by-layer (LBL) approach. The characterization results demonstrated that the multilayer system was successfully constructed and was capable of continuously releasing SP for almost 2 weeks. We further confirmed that MSCs grown on SP-modified Ti-based substrates showed improved migration capabilities as well as enhanced secretion of matrix metalloproteinases (MMP2, MMP9), rather than enhanced MSC proliferation and differentiation in vitro. In the CD29(+)/CD90(+) double immunofluorescence assay, the Ti/LBL-SP group showed the highest number of MSCs migrating to the peri-implant area after implantation. Consistently, the Ti/LBL-SP implants also significantly enhanced new bone formation according to the results of micro-CT scanning analysis, H&E staining, Masson's trichrome staining and immunohistochemical staining. The obtained results reveal that SP-modified Ti-based substrates were beneficial for bone formation via recruiting endogenous MSCs.

Pharmacological treatments for non-alcoholic steatohepatitis (NASH) are still unsatisfactory. Fibrosis is the most significant predictor of mortality and many anti-fibrotic agents are under evaluation. Herein, we assessed in vitro the effects of the FXR agonist obeticholic acid (OCA) and the dual FXR/TGR5 agonist INT-767 in a well-established co-culture NASH model. Co-cultures of human hepatoma and hepatic stellate (HSCs) cells were exposed to free fatty acids (FFAs) alone or in combination with OCA or INT-767. mRNA expression of HSCs activation markers and FXR engagement were evaluated at 24, 96 and 144 hours. Collagen deposition and metalloproteinase 2 and 9 (MMP2-9) activity were compared to tropifexor and selonsertib. FFAs induced collagen deposition and MMP2-9 activity reduction. Cotreatment with OCA or INT-767 did not affect ACTA2 and COL1A1 expression, but significantly reduced FXR and induced SHP expression, as expected. OCA induced a dose-dependent reduction of collagen and induced MMP2-9 activity. Similarly, INT-767 induced collagen reduction at 96 h and a slight increase in MMP2-9. Tropifexor and Selonsertib were also effective in collagen reduction but showed no modulation of MMP2-9. All tested compounds reduced collagen deposition. OCA exerted a more potent and long-lasting effect, mainly related to modulation of collagen turn-over and MMP2-9 activity.