Compressive loading of the murine tibia reveals site-specific micro-scale differences in adaptation and maturation rates of bone

Abstract

SummaryLoading increases bone mass and strength in a site-specific manner; however, possible effects of loading on bone matrix composition have not been evaluated. Site-specific structural and material properties of mouse bone were analyzed on the macro- and micro/molecular scale in the presence and absence of axial loading. The response of bone to load is heterogeneous, adapting at molecular, micro-, and macro-levels.IntroductionOsteoporosis is a degenerative disease resulting in reduced bone mineral density, structure, and strength. The overall aim was to explore the hypothesis that changes in loading environment result in site-specific adaptations at molecular/micro- and macro-scale in mouse bone.MethodsRight tibiae of adult mice were subjected to well-defined cyclic axial loading for 2 weeks; left tibiae were used as physiologically loaded controls. The bones were analyzed with μCT (structure), reference point indentation (material properties), Raman spectroscopy (chemical), and small-angle X-ray scattering (mineral crystallization and structure).ResultsThe cranial and caudal sites of tibiae are structurally and biochemically different within control bones. In response to loading, cranial and caudal sites increase in cortical thickness with reduced mineralization (−14 and −3%, p < 0.01, respectively) and crystallinity (−1.4 and −0.3%, p < 0.05, respectively). Along the length of the loaded bones, collagen content becomes more heterogeneous on the caudal site and the mineral/collagen increases distally at both sites.ConclusionBone structure and composition are heterogeneous, finely tuned, adaptive, and site-specifically responsive at the micro-scale to maintain optimal function. Manipulation of this heterogeneity may affect bone strength, relative to specific applied loads.Electronic supplementary materialThe online version of this article (doi:10.1007/s00198-016-3846-6) contains supplementary material, which is available to authorized users.

Murine Axial Compression Tibial Loading Model to Study Bone Mechanobiology: Implementing the Model and Reporting Results

“…In addition to altering bone mass and microstructure, some studies have indicated that mechanical loading can also alter bone mineral and matrix properties . The material bone mineral density or so‐called tissue mineral density (TMD) represents a volume of bone matrix that does not include marrow spaces, osteonal canals, lacunae or canaliculi, thus reflecting the degree of mineralization of organic bone matrix.…”

αSMA Osteoprogenitor Cells Contribute to the Increase in Osteoblast Numbers in Response to Mechanical Loading

“…Mechanical loading causes a rapid anabolic response in specific regions of the periosteum [3][4][5][6]. However, the origin of the cells that contribute to new osteoblast formation in this setting is not well defined.…”

“…The bone anabolic response to loading is site-specific, where most bone formation is seen at the periosteal caudal site [3,26]. Therefore, we investigated the number of osteoblasts and their origin at the periosteal caudal site and compared it to the cranial surface where less bone is formed in response to load.…”

“…1d). In response to axial mechanical loading, bone formation is induced at both these sites, but the response is stronger at the caudal than the cranial site [3,4,26]. For the single loading study, nuclei were counted manually in the ROIs using Zen software (Zeiss), followed by determination of the number of cells expressing one or more fluorescent labels.…”

“…Load is sensed by bone cells as increased strain and results in modeling/remodeling processes that alter the bone architecture and form bones that are able to resist the habitual loads that are placed upon them. The increased bone formation is strain-dependent and site-specific; in response to axial loading of the mouse tibia, most bone is formed at the caudal periosteal site of the loaded bone [3][4][5][6]. Osteoblast numbers also increase following loading both in vivo [7,8] and in vitro [7,9].…”