Mesenchymal stem cells (MSCs) have been extensively explored as a promising therapeutic agent in the field of bone tissue engineering due to their osteogenic differentiation ability. In this study, the osteogenic differential ability and the effect of fibronectin and laminin on the osteogenic differentiation in four types of MSCs derived from placental tissue are compared to determine the ideal source for bone reconstruction tissue engineering. The present study examines the osteogenic differentiation levels of four types of MSCs using alizarin red staining and quantifies the calcium levels and alkaline phosphatase (ALP) activity. In addition, this study examines the osteoblast differentiation protein markers osterix, collagen I, osteopontin, and osteocalcin using a Western blot assay. qPCR and EdU labeling assays were employed to identify the kinetics of osteogenic differentiation. Calcium deposit levels, ALP activity, and osteopontin and osteocalcin concentrations were determined to confirm the role of Extracellular matrix (ECM) components role on the osteogenic differentiation of MSCs. The data demonstrated that MSCs isolated from different layers of placenta had different potentials to differentiate into osteogenic cells. Importantly, AM-MSCs and UC-MSCs differentiated into the osteoblast stage more efficiently and quickly than CM-MSCs and DC-MSCs, which was associated with a decrease in their proliferation ability. Among the different types of MSCs, AM-MSCs and UC-MSCs had a higher osteogenic differentiation potential induced by fibronectin due to enhanced phosphorylation during the Akt and ERK pathways. Taken together, these results indicate that AM-MSCs and UC-MSCs possess a higher osteogenic potential, and fibronectin can robustly enhance the osteogenic potential of the Akt and ERK pathways.

Cutaneous-wound healing requires a coordinated reaction of multiple cells, including interstitial cells. Impaired recovery of cutaneous wounds can lead to various adverse health outcomes. Kangfuxin (KFX), an extract obtained from Periplaneta americana, is beneficial in cutaneous-wound healing. In this study, we isolated dermal cells from suckling mice and established a mouse model of cutaneous injury to evaluate the therapeutic effects of KFX. Cell biology experiments indicated that treatment with KFX improved cell proliferation and migration and also repaired cutaneous wounds in the animal model. Activation of the signal transducer and activator of transcription 3 (STAT3) signaling pathway was the core molecular mechanism of KFX. Our study provides a theoretical and practical basis for the clinical application of KFX in cutaneous-wound healing.

Background: Osteoporosis is a systemic bone disease characterized by bone loss and microstructural degeneration. Recent preclinical and clinical trials have further demonstrated that the transplantation of mesenchymal stem cells (MSCs) derived from human adipose tissue (AD), dental pulp (DP), placental amniotic membrane (AM), and umbilical cord (UC) tissues can serve as an effective form of cell therapy for osteoporosis. However, MSC-mediated osteoimmunology and the ability of these cells to regulate osteoclast-osteoblast differentiation varies markedly among different types of MSCs.Methods: In this study, we investigated whether transplanted allogeneic MSCs derived from AD, DP, AM, and UC tissues were able to prevent osteoporosis in an ovariectomy (OVX)-induced mouse model of osteoporosis. The homing and immunomodulatory ability of these cells as well as their effects on osteoblastogenesis and the maintenance of bone formation were compared for four types of MSCs to determine the ideal source of MSCs for the cell therapy-based treatment of OVX-induced osteoporosis. The bone formation and bone resorption ability of these four types of MSCs were analyzed using micro-computed tomography analyses and histological staining. In addition, cytokine array-based analyses of serological markers and bioluminescence imaging assays were employed to evaluate cell survival and homing efficiency. Immune regulation was determined by flow cytometer assay to reflect the mechanisms of osteoporosis treatment.Conclusion: These analyses demonstrated that MSCs isolated from different tissues have the capacity to treat osteoporosis when transplanted in vivo. Importantly, DP-MSCs infusion was able to maintain trabecular bone mass more efficiently with corresponding improvements in trabecular bone volume, mineral density, number, and separation. Among the tested MSC types, DP-MSCs were also found to exhibit greater immunoregulatory capabilities, regulating the Th17/Treg and M1/M2 ratios. These data thus suggest that DP-MSCs may represent an effective tool for the treatment of osteoporosis.

Adipose-derived mesenchymal stem cells (ADSCs) have been extensively explored as a promising therapeutic agent due to their differentiation, proliferation and migration abilities. The epigenetic mechanisms that regulate the fate of mesenchymal stem cells (MSCs) have been described in detail. However, the epigenetic modulation of ADSCs proliferation and migration is poorly understood. The present study examined histone demethylases roles and expression by RT-PCR, as well as through siRNA screening and ChIP-qPCR assay. Cellular proliferation and migration assays were employed in shRNA-mediated JMJD6 knockdown and control ADSCs. PDE1C inhibition studies were conducted to confirm its role in JMJD6-mediated epigenetic regulation of ADSCs. The data demonstrate that the histone demethylase JMJD6 plays a critical role in regulating the proliferation and migration of ADSCs by removing H4R3me2a at the promoter regions of PDEC1 and suppressing PDEC1 expression. Importantly, the depletion of JMJD6 in ADSCs significantly increased cellular proliferation and motility, which was associated with increases in PDE1C expression and decreases in the levels of both cAMP and cGMP. The increase in proliferation and migration was reversed by treatment with a PDE1C inhibitor, suggesting that JMJD6 attenuates the proliferation and migration of ADSCs as an epigenetic regulator and PDE1C partially contributes to the JMJD6-mediated regulation. Taken together, our results indicate for the first time that JMJD6 plays an important role in the regulation of ADSCs proliferation and migration through the modulation of PDE1C expression.