BackgroundOsteoarticular tuberculosis is an osteolytic lesion caused by Mycobacterium tuberculosis (MTB). Inflammatory factors such as TNF-α play a critical role in anti-tuberculosis immunity by regulating osteoblast and osteoclast functions. Both TGF-β and IL-10 have immune suppression effects to downregulate secretion and release of inflammatory factors, such as TNF-α, that play roles in regulating osteoblast and osteoclast functions. This study thus investigated the effects of osteoclast with modified TGF-β and IL-10 gene expression on MTB-induced osteoclast formation and bone absorption.Material/MethodsBone marrow mononuclear cells were induced to differentiate into osteoblasts and osteoclasts in vitro to generate a co-culture system. MTB powder lysed by ultrasound (Mt sonicate) were added in gradients to observe osteoblast formation and osteoclast absorption. Cell apoptosis was measured by flow cytometry, while ELISA was used assess TNF-α, TGF-β, and IL-10. Viral vectors carrying TGF-β or IL-10 gene were used to transfect osteoclasts, followed by ELISA assay. Bone absorption and osteoblast apoptosis were compared among groups.ResultsMt sonicate significantly facilitated osteoclast formation and bone formation. It upregulated contents of TNF-α, TGF-β, and IL-10, induced osteoblast apoptosis, enhanced RANKL expression in osteoblasts, and decreased OPG expression. Overexpression of TGF-β and/or IL-10 significantly decreased its upregulation effect on TNF-α by Mt sonicate, and hindered Mt sonicate-induced osteoblast apoptosis, osteoclast formation, and bone absorption.ConclusionsOverexpression of TGF-β and IL-10 significantly inhibits TMB-induced TNF-α synthesis and release, suppresses osteoblast apoptosis, and hinders osteoclast formation and bone absorption.

Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents. microRNAs (miRNAs) have previously been reported to be involved in the carcinogenesis and progression of OS, and may be useful prognostic markers or therapeutic targets for patients with OS. miRNA‑130a has been previously studied in multiple types of human cancer. However, its expression and function in OS has not been well documented. The aim of the present study was to investigate the expression, biological functions and molecular mechanisms underlying the effect of miR‑130a in OS. miR‑130a was significantly downregulated in OS tissues and cell lines compared with normal bone tissue and a normal osteoblast cell line. miR‑130a expression levels was significantly negatively correlated with the clinical stage and metastasis of OS. Further studies indicated that overexpression of miR‑130a inhibited OS cell proliferation, migration and invasion in vivo. In terms of the mechanisms underlying this effect, zinc finger E‑box binding homeobox 1 (ZEB1) was demonstrated to act as a direct target of miR‑130a in OS. Furthermore, downregulation of ZEB1 by interference with small interfering RNA mimicked the effects of transfection with an miR‑130a mimic in OS. In conclusion, these results demonstrated that miR‑130a functioned as a tumor suppressor in OS, partially via targeting ZEB1, suggesting that miR‑130a may be considered as a target for the treatment of patients with OS.

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