Molecular Mechanism of the Life and Death of the Osteoclast

Abstract

The life span of osteoclasts is critically regulated by various cytokines, and therapeutics such as bisphosphonates act directly on osteoclasts and induce apoptosis of the cells. This article will focus on the molecular mechanism of osteoclast apoptosis and summarize the recent advances in this field with an emphasis on the role of intracellular signaling pathways.

Sinomenine induces apoptosis in RAW 264.7 cell-derived osteoclasts in vitro via caspase-3 activation

“…Osteoclasts are a type of multinuclear terminal cell, which have a limited life span [4] . Regulation of osteoclast apoptosis makes possible the prospect of osteoclast-targeted therapy as a novel treatment strategy for bone disorders [21,22] .…”

“…factors, such as receptor activator of NF-κB ligand (RANKL) [4] . The regulation of osteoclast apoptosis influences bone resorptive activity and bone homeostasis, which can be a potential therapeutic target [5] .…”

Intracellular and Extracellular ATP Coordinately Regulate the Inverse Correlation between Osteoclast Survival and Bone Resorption

“…Because massive apoptosis in Tfam knock-out embryos was reported at embryonic day 9.5 and increased apoptosis in the heart of the tissue-specific Tfam knockouts was previously reported (13, 34), we next examined the role of Tfam in osteoclast survival. Mature osteoclasts undergo spontaneous apoptosis without any cytokines or supporting cells (3). After the removal of M-CSF and RANKL, ϳ80% of normal Tfam flox/flox osteoclasts died spontaneously within 24 h (Fig.…”

A2B Adenosine Receptor Stimulation Down-regulates M-CSF-mediated Osteoclast Proliferation

“…ERK1/2 MAP kinase and PI3K/Akt are key mediators of M-CSF signaling for osteoclast proliferation (Ross, 2006;Bradley et al, 2008;Gingery et al, 2003). The Akt pathway in particular prevents the activation of apoptotic signaling pathways and promotes cell cycle progression (Xing and Boyce, 2005;Tanaka et al, 2006;Gingery et al, 2003). Interestingly, A2BAR stimulation …”

“…Binding of M-CSF to c-Fms, an M-CSF receptor, autophosphorylates seven tyrosine residues in the cytoplasmic domain of the receptor (Ross, 2006;Faccio et al, 2007;Pixley et al, 2004); this stimulates a signaling cascades that lead to the proliferation, survival and differentiation of osteoclasts (Pixley et al, 2004;Bradley et al, 2008 (Ross, 2006;Pixley et al, 2004;Bradley et al, 2008). Especially, Akt pathway transduces anti-apoptotic signals by preventing the activation of the apoptotic signaling pathways and facilitates cell cycle progression (Xing and Boyce, 2005;Tanaka et al, 2006;Gingery et al, 2003).…”