Compressive mechanical force augments osteoclastogenesis by bone marrow macrophages through activation of c‐Fms‐mediated signaling

Abstract

Little is known about the effects of mechanical forces on osteoclastogenesis by bone marrow macrophages (BMMs) in the absence of mechanosensitive cells, including osteoblasts and fibroblasts. In this study, we examined the effects of mechanical force on osteoclastogenesis by applying centrifugal force to BMMs using a horizontal microplate rotor. Our findings, as measured by an in vitro model system, show that tumor necrosis factor (TNF)-α is capable of inducing osteoclast differentiation from BMMs and bone resorption in the presence of macrophage-colony stimulating factor (M-CSF) and is further facilitated by receptor activator of nuclear factor-kappaB (NF-κB) ligand (RANKL). Application of force to BMMs accelerated TNF-α-induced osteoclastogenesis; this was inhibited either by anti-TNF-α or anti-TNF-α receptor but not by OPG. TNF-α also increased c-Fms expression at both mRNA and protein levels in BMMs. An anti-c-Fms antibody completely inhibited osteoclast differentiation and bone resorption induced by TNF-α but partially blocked osteoclastogenesis stimulated in combination with RANKL. These results suggest that TNF-α (in the presence of M-CSF) is capable of inducing osteoclastogenesis from BMMs, and that osteoclastogenesis is significantly stimulated by force application through the activation of c-Fms-mediated signaling. Overall, the present study reveals the facilitating effect of mechanical force on osteoclastic differentiation from BMMs without the addition of mechanosensitive cells.

Acteoside Suppresses RANKL-Mediated Osteoclastogenesis by Inhibiting c-Fos Induction and NF-κB Pathway and Attenuating ROS Production

“…TNF-α can induce osteoclastogenesis independent of RANKL-RANK signaling [37]. IL-1 is a potent mediator of pathological bone destruction induced by estrogen deficiency or inflammation [7].…”

Human periodontal ligament fibroblasts stimulate osteoclastogenesis in response to compression force through TNF-α-mediated activation of CD4+ T cells

“…TNF-a is also capable of inducing osteoclast differentiation from BMM and bone resorption in the presence of M-CSF, a process that is further facilitated by RANKL [Cho et al, 2010]. In order to verify the roles of TNF-a on lymphocytes in the production of OPG and RANKL, the cultures of Jurkat or BJAB alone, or the co-cultures of these cells were exposed to 10 ng/ml TNF-a.…”

“…Bone marrow cells were obtained from 6-to 8-week-old BALB/c mice and cultured according to methods described elsewhere [Cho et al, 2010]. Animal care and use was approved by the Chonbuk National University Committee on Ethics in the Care and Use of Laboratory Animals (CBU 2010-0007).…”

Biophysical regulation of cancer stem/initiating cells: Implications for disease mechanisms and translation

“…Over the past two decades, it has become clear that the behavior of a wide range of cell types is sensitive to mechanical inputs encoded within the tissue environment [41–45]. Mechanotransductive pathways contribute to many aspects of normal physiology, ranging from developmental morphogenesis to adult tissue repair and regeneration [46–48].…”