Journal
MEDICAL SCIENCE MONITOR
Volume 24, Issue -, Pages 5200-5207Publisher
INT SCIENTIFIC INFORMATION, INC
DOI: 10.12659/MSM.909720
Keywords
Gene Expression Profiling; Receptors, Interleukin-10; Tuberculosis, Avian
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Background: Osteoarticular tuberculosis is an osteolytic lesion caused by Mycobacterium tuberculosis (MTB). Inflammatory factors such as TNF-alpha play a critical role in anti-tuberculosis immunity by regulating osteoblast and osteoclast functions. Both TGF-beta and IL-10 have immune suppression effects to downregulate secretion and release of inflammatory factors, such as TNF-alpha, that play roles in regulating osteoblast and osteoclast functions. This study thus investigated the effects of osteoclast with modified TGF-beta and IL-10 gene expression on MTB-induced osteoclast formation and bone absorption. Material/Methods: Bone 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-alpha, TGF-beta, and IL-10. Viral vectors carrying TGF-beta or IL-10 gene were used to transfect osteoclasts, followed by ELISA assay. Bone absorption and osteoblast apoptosis were compared among groups. Results: Mt sonicate significantly facilitated osteoclast formation and bone formation. It upregulated contents of TNF-alpha, TGF-beta, and IL-10, induced osteoblast apoptosis, enhanced RANKL expression in osteoblasts, and decreased OPG expression. Overexpression of TGF-beta and/or IL-10 significantly decreased its upregulation effect on TNF-alpha by Mt sonicate, and hindered Mt sonicate-induced osteoblast apoptosis, osteoclast formation, and bone absorption. Conclusions: Overexpression of TGF-beta and IL-10 significantly inhibits TMB-induced TNF-alpha synthesis and release, suppresses osteoblast apoptosis, and hinders osteoclast formation and bone absorption.
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