Abstract
Seed cells - mesenchymal stem cells (MSCs) - appear to be an attractive tool in the context of tissue engineering. Bone marrow represents the main source of MSCs for both experimental and clinical studies. However, the number limitation of bone marrow MSCs (BMSCs) and decreased function caused by proliferation make the search for adequate alternative sources of these cells for autologous and allogenic transplant necessary. This study was aimed to investigate the roles of cajanine isolated from the extracts of Cajanus cajan L. Millsp. in the proliferation and differentiation of BMSCs, and to discover the mechanism of proliferation of BMSCs promoted by cajanine. Bone marrow mesenchymal stem cells were cultured in high-glucose Dulbecco's Modified Eagle's Medium (DMEM) and osteogenic differentiation was induced by adding dexamethasone, ascorbic acid and β-glycerophosphate supplements. Bone marrow MSCs were cultured in medium without cajanine or supplemented with cajanine. The information about the proliferation and osteogenic differentiation of BMSCs was collated. The osteogenic differentiation potential of BMSCs was also assessed at the 3rd passage by Von Kossa staining. To observe cell signal transduction changes of BMSCs after culturing them with cajanine for 24 h, the western blot analysis was performed to detect phosphorylated cell cycle proteins and activated cyclins. After osteogenic induction, the differentiation of BMSCs was accelerated by cajanine treatment. Osteogenesis markers were upregulated by cajanine treatment at both protein and mRNA levels. Cajanine obviously promoted the proliferation of BMSCs. After BMSCs were cultured with cajanine for 24 h, the cell cycle regulator proteins were phosphorylated or upregulated. Cajanine can promote the expansion efficiency of BMSCs, at the same time keeping their multi-differentiation potential. Cajanine can activate the cell cycle signal transduction pathway, thus inducing cells to enter the G1/S phase and accelerating cells entering the G2/M phase. This study can contribute to the development of cajanine-based drugs in tissue engineering.
Highlights
Cajanus cajan is a perennial legume from the family Fabaceae.[1]
Cajanine promotes the osteogenic differentiation of bone marrow mesenchymal stem cells It has been well recognized that the human bone marrow stroma contains multipotent mesenchymal cells that give rise to adipocytes and osteoblasts, as well as many other lineages.[9]
To assess the roles of cajanine in the differentiation of bone marrow MSCs (BMSCs), we started to investigate whether cajanine isolated from the plant Cajanus cajan L
Summary
Cajanus cajan (cajanine) is a perennial legume from the family Fabaceae.[1]. It is extracted from pigeon pea leaves and has been reported to exhibit a variety of bioactivities, including antimalaria, hypolipidemia and cytotoxicity effects, as well as reducing bone loss and promoting bone-like tissue formation.[1,2,3,4,5,6,7] a recent study revealed that cajanine could increase tibial bone density and improve bone metabolism as well as lipid metabolism in ob/ob mice with osteoporosis and hyperlipidemia symptoms, indicating that cajanine might be a promising drug candidate due to its broad range of bioactivities.[8]Mesenchymal stem cells (MSCs) are a small population of multipotent stromal cells that are present in practically all tissues.[9]. The transforming growth factor-β (TGF-β) signal pathway has been studied as a key regulator in the self-renewal, maintenance and differentiation of stem cells.[10,11,12] It has been reported that TGF-β1 plays an important role in cartilage development and is an important chondrogenic factor.[12,13] some studies have demonstrated that cajanine has anti-tumor and anti-oxidant functions.[14] Despite evidence revealing that cajanine has potential to be a therapeutic agent, the detailed mechanisms of anti-tumor effects are still under investigation. Bone marrow represents the main source of MSCs for both experimental and clinical studies. The number limitation of bone marrow MSCs (BMSCs) and decreased function caused by proliferation make the search for adequate alternative sources of these cells for autologous and allogenic transplant necessary
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