TNF-a was originally described as an endotoxin-induced, macrophage-derived factor that promotes hemorrhagic necrosis of solid tumors and the cachexia of chronic infections. TNF-a has also been implicated in a range of inflammatory, infectious, and malignant disorders. At the cellular level, TNF-a modulates a broad spectrum of responses including inflammation, immunoregulation, proliferation, apoptosis, and antiviral activity. In bone, the cytokine inhibits extracellular matrix deposition, stimulates matrix metalloprotease synthesis, and enhances production of osteoclastogenic cytokines such as M-CSF and RANKL. Chronic exposure to TNFa in vivo increases osteoclastogenesis through two distinct mechanisms. TNFa first affects osteoclastogenesis at the osteoclast precursor stage in the bone marrow by priming these cells to differentiate into cFms+/CD11b+/RANK+/- osteoclast progenitors via a RANKL/RANK independent mechanism. These osteoclast precursors then enter the blood and peripheral tissues where they differentiate into mature osteoclasts in the presence of RANKL, and this process is accelerated by TNF. The role of TNF at this later stage of osteoclast differentiation is RANKL/RANK dependent. Importantly, TNF-a promotes bone resorption both in vitro and in vivo by enhancing the proliferation and differentiation of osteoclast precursors.
原厂资料：
Description:
TNF-a was originally described as an endotoxin-induced, macrophage-derived factor that promotes hemorrhagic necrosis of solid tumors and the cachexia of chronic infections. TNF-a has also been implicated in a range of inflammatory, infectious, and malignant disorders. At the cellular level, TNF-a modulates a broad spectrum of responses including inflammation, immunoregulation, proliferation, apoptosis, and antiviral activity. In bone, the cytokine inhibits extracellular matrix deposition, stimulates matrix metalloprotease synthesis, and enhances production of osteoclastogenic cytokines such as M-CSF and RANKL. Chronic exposure to TNFa in vivo increases osteoclastogenesis through two distinct mechanisms. TNFa first affects osteoclastogenesis at the osteoclast precursor stage in the bone marrow by priming these cells to differentiate into cFms+/CD11b+/RANK+/- osteoclast progenitors via a RANKL/RANK independent mechanism. These osteoclast precursors then enter the blood and peripheral tissues where they differentiate into mature osteoclasts in the presence of RANKL, and this process is accelerated by TNF. The role of TNF at this later stage of osteoclast differentiation is RANKL/RANK dependent. Importantly, TNF-a promotes bone resorption both in vitro and in vivo by enhancing the proliferation and differentiation of osteoclast precursors.
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