Mechanical vibration inhibits osteoclast formation by reducing DC-STAMP receptor expression in osteoclast precursor cells

Abstract

It is well known that physical inactivity leads to loss of muscle mass, but it also causes bone loss. Mechanistically, osteoclastogenesis and bone resorption have recently been shown to be regulated by vibration. However, the underlying mechanism behind the inhibition of osteoclast formation is yet unknown. Therefore, we investigated whether mechanical vibration of osteoclast precursor cells affects osteoclast formation by the involvement of fusion-related molecules such as dendritic cell-specific transmembrane protein (DC-STAMP), and P2X7 receptor (P2X7R). RAW264.7 (a murine osteoclastic-like cell line) cells were treated with 20 ng/ml receptor activator of NF-κB ligand (RANKL). For 3 consecutive days, the cells were subjected to 1 hour of mechanical vibration with 20 µm displacement at a frequency of 4 Hz and compared to the control cells that were treated under the same condition but without the vibration. After 5 days of culture, osteoclast formation was determined. Gene expression of DC-STAMP and P2X7R by RAW264.7 cells were determined after 1 hour mechanical vibration, while protein production of the DC-STAMP was determined after 6 hours of post incubation after vibration. As a result, mechanical vibration of RAW264.7 cells inhibited the formation of osteoclasts. Vibration down-regulated DC-STAMP gene expression by 1.6-fold in the presence of RANKL and by 1.4-fold in the absence of RANKL. Additionally, DC-STAMP protein production was also down-regulated by 1.4-fold in the presence of RANKL and by 1.2-fold in the absence of RANKL in RAW264.7 cells in response to mechanical vibration. However, vibration did not affect P2X7R gene expression. Mouse anti-DC-STAMP antibody inhibited osteoclast formation in the absence of vibration. Our results suggest that mechanical vibration of osteoclast precursor cells reduce DC-STAMP expression in osteoclast precursor cells leading to the inhibition of osteoclast formation.

The bio‐response of osteocytes and its regulation on osteoblasts under vibration

“…In recent decades, some experiments have been conducted to investigate the effect of LMHF vibration on bone cells. The results showed that bone formation by osteoblasts was promoted (Dumas et al, ) and the bone resorption by osteoclasts was inhibited by LMHF vibration (Kulkarni et al, ). Osteocytes, the mechanosensors in bone, have also been demonstrated to be affected by LMHF vibration.…”

Mechanisms of mechanically induced Osteoclastogenesis : in a novel in vitro model for bone implant loosening

“…However, the direct effect of mechanical loading on osteoclast formation and activity have also been shown: In murine monocyte/macrophage cell line RAW264.7, a 10% elongation at a frequency of 0.5 Hz for 48h resulted in a decrease in osteoclasts due to a decrease in osteoclast-specific genes (TRAP, MMP-9, CathK, and CTR) [152]. Another study on RAW264.7 cells showed that stimulation for one hour with mechanical vibration (20 µm displacement at a frequency of 4 Hz) for three consecutive days inhibited osteoclast formation due to down-regulated DC-STAMP, preventing the fusion process of osteoclast precursors [106]. Bone marrow cells from male C57Bl/6 mice subjected to 5% elongation at a frequency of 0.167 Hz during early phases of osteoclast formation (day 2-4 in a 7-day culture) reduce the number of multinucleated, TRAP+ osteoclasts [153].…”

“…chewing (vibrational) load, low-magnitude high-frequency vibration (LMHFV), intermitted compressive force, etc. ), mechanical loading in a physiological range led to the reduction of osteoclast formation or osteoclast resorbing activity [106][107][108]. (2)Unloading-driven alterations in the mechanical loading show a significant reduction of bone mass in weight-bearing bones [109].…”

The effects of acoustic vibration on fibroblast cell migration

“…At the cellular level Aryaei and Jayasuriya [10] found that mechanical stimulation can be used to improve osteoblast attachment and proliferation [10]. Kulkarni et al [11], found that mechanical stimulation can inhibit bone reabsorption. Similarly, Wu et al [12] found that mechanical stimulation produced an anabolic effect on bone through the inhibition of osteoclast differentiation and Kim et al [12], found that low-magnitude high-frequency (LMHF) mechanical stimulation enables the osteogenic process of human mesenchymal stromal cells (hMSCs).…”