Force-Induced Osteoclast Apoptosis In Vivo Is Accompanied by Elevation in Transforming Growth Factor β and Osteoprotegerin Expression

Abstract

The mechanism controlling the disappearance of osteoclasts from bone surfaces after bone resorption in vivo is largely unknown. This is because there is no suitable experimental system to trace the final fate of osteoclasts. Here, we used an experimental model of tooth movement in rats to show that preexisting osteoclasts disappeared from the bone surface through apoptosis during a force-induced rapid shift from bone resorption to formation. On the distal alveolar bone surface of the maxillary molar in growing rats, many mature osteoclasts were present. When light tensional force was applied to the bone surface through an orthodontic appliance, these preexisting osteoclasts gradually disappeared. One day after the application of force, about 24% of the osteoclasts exhibited apoptotic morphology and the proportion of apoptotic cells was increased to 41% by day 2, then decreased afterward. These changes were undetectable on the control distal alveolar bone surface, which is free from tensional force. As shown by in situ hybridization, a marked increase in transforming growth factor ␤1 (TGF-␤1) and osteoprotegerin (OPG) messenger RNA (mRNA) was observed in the stretched cells on the tensioned distal bone surface, simultaneously with the loss of osteoclasts. Both of these factors are known to have a negative effect on osteoclast recruitment and survival. As early as 2 days after force application, some of these stretched cells were identified as cuboidal osteoblasts showing intense signals for both factors. Our data suggest there may be a sequential link in tensional force applied on the bone lining cells, up-regulation of TGF-␤1/OPG, and disappearance of osteoclasts. (J Bone Miner Res 2000; 15:1924 -1934)

Bone ingrowth on the surface of endosseous implants. Part 2: Theoretical and numerical analysis

“…The mechanical environment, for example, can be one possible origin of cell stimulation. In fact, it is known that moderate mechanical loading stimulates two crucial phenomena in periimplant bone healing: osteogenic cell differentiation (Carter and Giori, 1991;Palma et al, 2005;Ignatius et al, 2005), quantified by α mb in our model, and growth factor secretion (Raab-Cullen et al, 1994;Yeh et al, 1994;Kobayashi et al, 2000), denoted by α 2 . According to these experimental results, an hypothetical rise of the level of mechanical stimulation would lead to an increase of χ and, thus, χ could be considered to some extent as a measure of mechanical stimulation (see Fig.…”

Osteocytes as mechanosensors in the inhibition of bone resorption due to mechanical loading

“…It has been shown that mechanical loading has the ability to suppress bone resorption (3,8,12,26). However, the cellular mechanism that underlies this anti-resorptive effect is not clear.…”

“…Physical loading and routine activities have been shown to inhibit bone resorption that would otherwise occur with disuse (3,8,12,26). However, the cellular mechanism underlying this phenomenon remains largely unknown.…”

Apoptosis in developmental and repair-related human tooth remodeling: A view from the inside

“…5). Several findings also indicate that compressive forces induce apoptosis [34,35], thus suggesting that external forces play a role in pulp volume reduction.…”