Osteoregulatory nature of mechanical stimuli: Function as a determinant for adaptive remodeling in bone

Rubin, Clinton T.; Lanyon, Lance E.

doi:10.1002/jor.1100050217

Cited by 478 publications

(209 citation statements)

References 17 publications

(7 reference statements)

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“…Where the stress was higher, there was periosteal or endosteal new bone formation and increased density [2]. In contrast to this, we did not find any stress-related changes in BMD around the component we used, and this differs from a previous report which found a linear relation between mechanical factors, such as stress and strain, and BMD [12].…”

Section: Discussioncontrasting

confidence: 99%

Changes in bone mineral density around a stable uncemented total hip arthroplasty

Korovessis

Piperos

Michael

et al. 1997

International Orthopaedics

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Section: Discussioncontrasting

confidence: 99%

Changes in bone mineral density around a stable uncemented total hip arthroplasty

Korovessis

Piperos

Michael

et al. 1997

International Orthopaedics

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“…Previous in vivo models demonstrate a positive linear relationship exists between applied strain magnitude and a change in bone mass (46,47). Additional studies showed that bone can recover its sensitivity to mechanical stimuli to the same degree as previous exposure to load with the inclusion of rest periods (48).…”

Section: Discussionmentioning

confidence: 92%

Adaptation of Connexin 43-Hemichannel Prostaglandin Release to Mechanical Loading

Siller-Jackson

Burra

et al. 2008

Journal of Biological Chemistry

154

179

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Bone tissues respond to mechanical loading/unloading regimens to accommodate (re)modeling requirements; however, the underlying molecular mechanism responsible for these responses is largely unknown. Previously, we reported that connexin (Cx) 43 hemichannels in mechanosensing osteocytes mediate the release of prostaglandin, PGE 2 , a crucial factor for bone formation in response to anabolic loading. We show here that the opening of hemichannels and release of PGE 2 by shear stress were significantly inhibited by a potent antibody we developed that specifically blocks Cx43-hemichannels, but not gap junctions or other channels. The opening of hemichannels and release of PGE 2 are magnitude-dependent on the level of shear stress. Insertion of a rest period between stress enhances this response. Hemichannels gradually close after 24 h of continuous shear stress corresponding with reduced Cx43 expression on the cell surface, thereby reducing any potential negative effects of channels staying open for extended periods. These data suggest that Cx43-hemichannel activity associated with PGE 2 release is adaptively regulated by mechanical loading to provide an effective means of regulating levels of extracellular signaling molecules responsible for initiation of bone (re)modeling.The skeleton regulates its architecture and mass to meet structural and metabolic needs. To fulfill its structural functions, this complex tissue must adapt to loading and unloading while simultaneously regulating the metabolic demands of the skeleton. Numerous in vivo animal studies show the essential role of mechanical loading for bone formation and remodeling; however, the underlying molecular mechanisms, in particular how bone cells adapt to mechanical stimulation, remain largely uncharacterized.When mechanical forces are applied to bone, several potential stimuli occur including changes in hydrostatic pressure, direct cell strain, fluid flow, and electric potentials. These changes lead to fluid movement through the bone (1-3). Shear stress induced by mechanical loading facilitates the exchange of nutrients and bone modulators, and elicits biochemical responses. Osteocytes are well positioned in the bone to sense the magnitude of mechanical strain and are essential for the skeleton adaptive response to load. Experimental studies have shown that osteocytes are sensitive to stress applied to both intact bone tissue and in cell culture (4 -6). Encased within mineralized tissue, their dendritic morphology allows them to connect through small tunnels called canaliculi to form a threedimensional network not only with adjacent osteocytes but also to connect to cells on the bone surface and bone marrow.Connexins (Cx), 2 gap junction-forming proteins, belong to a multigene family expressing four transmembrane domains. The regions corresponding to transmembrane and extracellular domains are highly conserved. Cx43 has been identified in most types of bone cells (7-13) and is the major connexin expressed in osteocyte-like MLO-Y4 cells and primary osteocy...

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“…It is generally accepted that this relationship between bone morphology (density/micro-architecture) and loading is the result of a local load-adaptive bone remodeling process regulated and carried out by bone cells in such a way that bone tissue is added to high-load locations and removed from low-load locations ('Wolff's law') (Schulte et al 2011;Adams et al 1997;Forwood and Turner 1995;Goldstein et al 1991;Rubin and Lanyon 1987;Frost 1987;Wolff 1892). This implies that, eventually, all bone tissue should be loaded uniform, thus producing a bone morphology that is optimized for the external loading history that it is subjected to.…”

Section: Introductionmentioning

confidence: 99%

Bone morphology allows estimation of loading history in a murine model of bone adaptation

Christen

Rietbergen

Lambers

et al. 2011

Biomech Model Mechanobiol

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Bone adapts its morphology (density/microarchitecture) in response to the local loading conditions in such a way that a uniform tissue loading is achieved ('Wolff's law'). This paradigm has been used as a basis for bone remodeling simulations to predict the formation and adaptation of trabecular bone. However, in order to predict bone architectural changes in patients, the physiological external loading conditions, to which the bone was adapted, need to be determined. In the present study, we developed a novel bone loading estimation method to predict such external loading conditions by calculating the loading history that produces the most uniform bone tissue loading. We applied this method to murine caudal vertebrae of two groups that were in vivo loaded by either 0 or 8 N, respectively. Plausible load cases were sequentially applied to micro-finite element models of the mice vertebrae, and scaling factors were calculated for each load case to derive the most uniform tissue strainenergy density when all scaled load cases are applied simultaneously. The bone loading estimation method was able to predict the difference in loading history of the two groups and the correct load magnitude for the loaded group. This result suggests that the bone loading history can be estimated from its morphology and that such a method could be useful for predicting the loading history for bone remodeling studies or at sites where measurements are difficult, as in bone in vivo or fossil bones.

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Osteoregulatory nature of mechanical stimuli: Function as a determinant for adaptive remodeling in bone

Cited by 478 publications

References 17 publications

Changes in bone mineral density around a stable uncemented total hip arthroplasty

Changes in bone mineral density around a stable uncemented total hip arthroplasty

Adaptation of Connexin 43-Hemichannel Prostaglandin Release to Mechanical Loading

Bone morphology allows estimation of loading history in a murine model of bone adaptation

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