Local Mechanical Stimuli Regulate Bone Formation and Resorption in Mice at the Tissue Level

Abstract

Bone is able to react to changing mechanical demands by adapting its internal microstructure through bone forming and resorbing cells. This process is called bone modeling and remodeling. It is evident that changes in mechanical demands at the organ level must be interpreted at the tissue level where bone (re)modeling takes place. Although assumed for a long time, the relationship between the locations of bone formation and resorption and the local mechanical environment is still under debate. The lack of suitable imaging modalities for measuring bone formation and resorption in vivo has made it difficult to assess the mechanoregulation of bone three-dimensionally by experiment. Using in vivo micro-computed tomography and high resolution finite element analysis in living mice, we show that bone formation most likely occurs at sites of high local mechanical strain (p<0.0001) and resorption at sites of low local mechanical strain (p<0.0001). Furthermore, the probability of bone resorption decreases exponentially with increasing mechanical stimulus (R2 = 0.99) whereas the probability of bone formation follows an exponential growth function to a maximum value (R2 = 0.99). Moreover, resorption is more strictly controlled than formation in loaded animals, and ovariectomy increases the amount of non-targeted resorption. Our experimental assessment of mechanoregulation at the tissue level does not show any evidence of a lazy zone and suggests that around 80% of all (re)modeling can be linked to the mechanical micro-environment. These findings disclose how mechanical stimuli at the tissue level contribute to the regulation of bone adaptation at the organ level.

Determination of hip-joint loading patterns of living and extinct mammals using an inverse Wolff’s law approach

“…3). Nevertheless, we know most bone formation takes place at high-load locations and most resorption at low-load locations (Schulte et al 2013), and this seems to be enough for our algorithm to reveal a reasonable loading history as demonstrated in the present and also earlier studies (Christen et al 2013b(Christen et al , 2012.…”

“…Osteocytes in the bone are capable of sensing local tissue loading and are thus considered to trigger bone adaptation according to mechanical loading. This process strives to create a state where all bone tissue is loaded as uniformly as possible in order to avoid peak loads and unnecessary weight (Barak et al 2011;Lambers et al 2011;Pontzer et al 2006;Roux 1881;Schulte et al 2013;Sugiyama et al 2012Sugiyama et al , 2010Wolff 1892). The formfunction relationship due to bone adaptation implies that it might be possible as well to reversely derive hip-joint loading patterns from the femoral head microstructure by finding a set of joint forces that produce such a state of uniform tissue loading.…”

A theory for bone resorption based on the local rupture of osteocytes cells connections: A finite element study

“…Small cracks, which grow under cyclic stresses by the mechanism of fatigue, can be detected and removed before they become long enough to be dangerous. Although assumed for a long time, the relationship between the locations of bone formation and resorption and the local mechanical environment is still under debate [30]. The lack of suitable imaging modalities for measuring bone formation and resorption in vivo has made it difficult to assess the bone formation and resorption experimentally.…”

Mechanical Signaling in NF1 Osteoblast Cells

“…In this model, the Nf1 gene has been knocked-out using the Cre-LoxP system under the control of 2.3 kb collagen1-alpha1 promoter (Col11), which is primarily expressed in osteoblast [23,25]. Our current view of the NF1 bone pathology, based on the analysis of osteoblast function, whether the imbalance of bone homeostasis and improper response of osteoblast cell to mechanical stress cause the NF1 skeletal manifestations [26][27][28][29][30][31][32][33][34][35].…”