Tumor Necrosis Factor-α Induces Differentiation of and Bone Resorption by Osteoclasts*
By Y. Azuma, K. Kaji, R. Katogi, S. Takeshita, A. Kudo. Journal of Biological Chemistry, 2000
769 citations recorded by the source corpus.
Osteoclast progenitors differentiate into mature osteoclasts in the presence of receptor activator of NF-κB (RANK) ligand on stromal or osteoblastic cells and monocyte macrophage colony-stimulating factor (M-CSF). The soluble RANK ligand induces the same differentiation in vitro without stromal cells. Tumor necrosis factor-α (TNF-α), a potent cytokine involved in the regulation of osteoclast activity, promotes bone resorption via a primary effect on osteoblasts; however, it remains unclear whether TNF-α can also directly induce the differentiation of osteoclast progenitors into mature osteoclasts. This study revealed that TNF-α directly induced the formation of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells (MNCs), which produced resorption pits on bone in vitro in the presence of M-CSF. The bone resorption activity of TNF-α-induced MNCs was lower than that of soluble RANK ligand-induced MNCs; however, interleukin-1β stimulated this activity of TNF-α-induced MNCs without an increase in the number of MNCs. In this case, interleukin-1β did not induce TRAP-positive MNC formation. The osteoclast progenitors expressed TNF receptors, p55 and p75; and the induction of TRAP-positive MNCs by TNF-α was inhibited completely by an anti-p55 antibody and partially by an anti-p75 antibody. Our findings presented here are the first to indicate that TNF-α is a crucial differentiation factor for osteoclasts. Our results suggest that TNF-α and M-CSF play an important role in local osteolysis in chronic inflammatory diseases.
Subfields: Molecular Biology, Oncology, Orthopedics and Sports Medicine
View Paper: https://www.semanticscholar.org/paper/a0c1e923b022b7d515117fe39a4a98acbcd6df9b
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Citations in the corpus
- Role of receptor activator of nuclear factor-κB ligand and osteoprotegerin in bone cell biology (2001, background): “However, the fact that RANK-deficient mice are resistant against the hypercalcemic and bone-resorptive effects of IL-1 and TNF-α [38], and that OPG can prevent bone loss in a model of adjuvant arthritis (which is characterized by local overproduction of IL-1 and TNF-α) [11] suggest only a minor and ”
- Mechanisms of TNF-α– and RANKL-mediated osteoclastogenesis and bone resorption in psoriatic arthritis (2003, positive): “The finding of RANK-positive mononuclear cells in the synovium, confirmed by elevated RANK mRNA expression in at least some of our PsA patients, was in line with previous studies that detected TRAP-positive cells in RA synovium and report that osteoclasts can be generated from RA synovium and bone (”
- IL-6, RANKL, TNF-alpha/IL-1: interrelations in bone resorption pathophysiology. (2004, background): “In contrary, it has been recently demonstrated that TNF- directly induces osteoclastogenesis in mouse [44,74] and human [73] marrow cultures.”