Osteoinductive accelerating potential of myxobacterial secondary metabolites

Hamide Parhizkari , Fatemeh Mohammadipanah , Mahshid Hodjat
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Abstract

The increased aging population demands improved osteoblast generation in vitro for clinical treatments. Myxobacteria synthesize a wide range of biologically active secondary metabolites with unique structural features that motivated their evaluation in this study for differentiation induction of bone marrow stem cells into osteoblasts. Calcium deposition and alkaline phosphatase (AKP) enzyme activity were quantitatively measured, and the expression of osteoblastic markers and calcium nodules was determined via alizarin red staining as differentiation markers. Results showed that a myxobacterial extract induced bone marrow stem cell differentiation by increasing AKP activity, calcium deposition, osteopontin (OPN), and osteocalcin (OCN) expression. Compared to conventional osteogenesis medium, Myxobacterium UTMC 4530 metabolite extract at 0.048 μg/ml, showed 27 % higher AKP activity, as well as 13 % and 7 % higher expression of the OCN and OPN genes, respectively. Despite ultralow concentrations, Myxobacterial extract induces a high level of differentiation, which may make it a valuable source of assessment for developing potent in vitro inducers of bone marrow stem cells which may have therapeutic potential in the future by promoting osteogenesis
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霉菌次生代谢物的骨诱导加速潜力
随着老龄化人口的增加,临床治疗需要改进体外成骨细胞的生成。粘菌能合成多种具有生物活性的次生代谢产物,其独特的结构特征促使本研究对其进行评估,以评估其在诱导骨髓干细胞分化为成骨细胞方面的作用。本研究对钙沉积和碱性磷酸酶(AKP)活性进行了定量测定,并通过茜素红染色确定了作为分化标志物的成骨细胞标志物和钙结节的表达。结果表明,粘杆菌提取物可通过增加AKP活性、钙沉积、骨生成素(OPN)和骨钙素(OCN)的表达来诱导骨髓干细胞分化。与传统的成骨培养基相比,UTMC 4530粘杆菌代谢物提取物的浓度为0.048微克/毫升时,其AKP活性提高了27%,OCN和OPN基因的表达也分别提高了13%和7%。尽管浓度极低,粘菌提取物仍能诱导高水平的分化,这可能使其成为开发骨髓干细胞体外诱导剂的宝贵评估来源。
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