Light-Controlled BMSC Sheet–Implant Complexes with Improved Osteogenesis via an LRP5/β-Catenin/Runx2 Regulatory Loop

Abstract

The combination of bone marrow mesenchymal stem cell (BMSC) sheets and titanium implants (BMSC sheet-implant complexes) can accelerate osseointegration. However, methods of fabricating BMSC sheet-implant complexes are quite limited, and the survival of BMSC sheet-implant complexes is one of the key barriers. Here, we show that a light-controlled fabricating system can generate less injured BMSC sheet-implant complexes with improved viability and osteogenesis and that noninvasive monitoring of the viability of BMSC sheet-implant complexes using a lentiviral delivery system is feasible. Enhanced green fluorescent protein- and luciferase-expressing BMSC sheets were used to track the viability of BMSC sheet-implant complexes in vivo. The experiments of micro-computed tomography analysis and hard tissue slices were performed to evaluate the osteogenic ability of BMSC sheet-implant complexes in vivo. The results showed that BMSC sheet-implant complexes survived for almost 1 month after implantation. Notably, BMSC sheet-implant complexes fabricated by the light-controlled fabricating system had upregulating expression levels of low-density lipoprotein-receptor-related protein 5 (LRP5), β-catenin, and runt-related transcription factor 2 (Runx2) compared to the complexes fabricated by mechanical scraping. Furthermore, we found that Runx2 directly bound to the rat LRP5 promoter and the LRP5/β-catenin/Runx2 regulatory loop contributed to the enhancement of the osseointegrating potentials. In this study, we successfully fabricated BMSC sheet-implant complexes with improved viability and osteogenesis and established a feasible, noninvasive, and continuous method for tracking BMSC sheet-implant complexes in vivo. Our findings lay the foundation for the application of BMSC sheet-implant complexes in vivo and open new avenues for engineered BMSC sheet-implant complexes.

Synergistic Effects of Erzhi Pill Combined With Methotrexate on Osteoblasts Mediated via the Wnt1/LRP5/β-Catenin Signaling Pathway in Collagen-Induced Arthritis Rats

“…Finally, b-catenin translocates into the nucleus and induces the expression of target genes, such as Runx2. In OB differentiation, Wnt1 (Laine et al, 2013), Wnt3a (Li et al, 2019), and Wnt5a (Wang et al, 2019) play dominant roles in activating b-catenin through the binding receptor LRP5 (Gong et al, 2001;Chang et al, 2014) with other molecules, thereby promoting the transcription of the differentiation factor Runx2 (Jiang et al, 2017). In this study, both EZP alone and MTX alone increased the gene expression of Wnt1, LRP5, and bcatenin, indicating that both agents target the Wnt1/LRP5/bcatenin pathway.…”

Additive-lathe 3D bioprinting of bilayered nerve conduits incorporated with supportive cells

“…GelMA was utilized as the inner layer material for cell encapsulation due to its superior biological properties [ 2 , 39 ]. Since the biological properties of GelMA were broadly tunable depending on DMS, as such, the optimized DMS of GelMA for cell proliferation must be determined before fabrication.…”

BMP2‐mimicking peptide modified with E7 coupling to calcined bovine bone enhanced bone regeneration associating with activation of the Runx2/SP7 signaling axis

“…Three‐week‐old male Sprague–Dawley (SD) rats were sacrificed for the isolation of BMSCs. And, BMSCs were aspirated from femurs and tibias as previously described . Cells were cultured in the alpha‐modified minimum essential medium (Jima, China) containing 10% fetal bovine serum (Gibco).…”

“…And, BMSCs were aspirated from femurs and tibias as previously described. 24 Cells were cultured in the alpha-modified minimum essential medium (Jima, China) containing 10% fetal bovine serum (Gibco). The third generations of BMSCs were used in the experiment.…”