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dc.contributor.authorMartin, Madge
dc.contributor.authorSansalone, Vittorio
dc.contributor.authorCooper, David ML
dc.contributor.authorForwood, Mark R
dc.contributor.authorPivonka, Peter
dc.date.accessioned2019-07-05T04:12:30Z
dc.date.available2019-07-05T04:12:30Z
dc.date.issued2019
dc.identifier.issn1617-7959
dc.identifier.doi10.1007/s10237-019-01158-w
dc.identifier.urihttp://hdl.handle.net/10072/386185
dc.description.abstractSignificant progress has been made to identify the cells and signaling molecules involved in the mechanobiological regulation of bone remodeling. It is now well accepted that osteocytes act as mechanosensory cells in bone expressing several signaling molecules such as nitric oxide (NO) and sclerostin (Scl) which are able to control bone remodeling responses. In this paper, we present a comprehensive multiscale computational model of bone remodeling which incorporates biochemical osteocyte feedback. The mechanostat theory is quantitatively incorporated into the model using mechanical feedback to control expression levels of NO and Scl. The catabolic signaling pathway RANK–RANKL–OPG is co-regulated via (continuous) PTH and NO, while the anabolic Wnt signaling pathway is described via competitive binding reactions between Wnt, Scl and the Wnt receptors LRP5/6. Using this novel model of bone remodeling, we investigate the effects of changes in the mechanical loading and hormonal environment on bone balance. Our numerical simulations show that we can calibrate the mechanostat anabolic and catabolic regulatory mechanisms so that they are mutually exclusive. This is consistent with previous models that use a Wolff-type law to regulate bone resorption and formation separately. Furthermore, mechanical feedback provides an effective mechanism to obtain physiological bone loss responses due to mechanical disuse and/or osteoporosis.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherSpringer
dc.relation.ispartofjournalBiomechanics and Modeling in Mechanobiology
dc.subject.fieldofresearchBiomedical Engineering
dc.subject.fieldofresearchMechanical Engineering
dc.subject.fieldofresearchcode0903
dc.subject.fieldofresearchcode0913
dc.titleMechanobiological osteocyte feedback drives mechanostat regulation of bone in a multiscale computational model
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.description.notepublicThis publication has been entered into Griffith Research Online as an Advanced Online Version.
gro.hasfulltextNo Full Text
gro.griffith.authorForwood, Mark R.


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