Mechanically induced bone formation is not sensitive to local osteocyte density in rat vertebral cancellous bone

Abstract

Osteocytes play an integral role in bone by sensing mechanical stimuli and releasing signaling factors that direct bone formation. The importance of osteocytes in mechanotransduction suggests that regions of bone tissue with greater osteocyte populations are more responsive to mechanical stimuli. To determine the effects of osteocyte population on bone functional adaptation we applied mechanical loads to the 8th caudal vertebra of skeletally mature female Sprague Dawley rats (6 months of age, n = 8 loaded, n = 8 sham controls). The distribution of tissue stress/strain within cancellous bone was determined using high-resolution finite element models, osteocyte distribution was determined using nano-computed tomography, and locations of bone formation were determined using three-dimensional images of fluorescent bone formation markers. Loading increased bone formation (3D MS/BS 10.82 ± 2.09% in loaded v. 3.17 ± 2.05% in sham control, mean ± SD). Bone formation occurred at regions of cancellous bone experiencing greater tissue stress/strain, however stress/strain was only a modest predictor of bone formation; even at locations of greatest stress/strain the probability of observing bone formation did not exceed 41%. The local osteocyte population was not correlated with locations of new bone formation. The findings support the idea that local tissue stress/strain influence the locations of bone formation in cancellous bone, but suggest that the size of the osteocyte population itself is not influential. We conclude that other aspects of osteocytes such as osteocyte connectivity, lacunocanilicular nano-geometry, and/or fluid pressure/shear distributions within the marrow space may be more influential in regulating bone mechanotransduction than the number of osteocytes. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:672-681, 2018.

Large-scale quantification of human osteocyte lacunar morphological biomarkers as assessed by ultra-high-resolution desktop micro-computed tomography

“…However, we were careful to create the best manual segmentation dataset possible for comparison. Hernandez et al have used similar accuracy comparisons in previous studies and in fact, achieve similar rates of TP, FP and FN to ours [49]. Interestingly, sample 3 in our accuracy calculation exhibited an inordinately low TPR and high FNR.…”

“…Therefore, our approach was to pragmatically locate a threshold that was intrinsically linked to the sample specific TMD distribution, compare the resulting lacunar identification with manual identification, and quantify the accuracy. Previous studies have tried similar individual threshold approaches, which are offset from a reference point of the TMD histogram such as the mean [50], but we found our specific images responded best to selecting the TMD histogram critical point as a landmark for segmentation (Figure S1). In addition, the critical point is a clear and calculable landmark on every TMD histogram, which is less prone to error than an offset.…”

Mechanical Stimuli in the Local In Vivo Environment in Bone: Computational Approaches Linking Organ-Scale Loads to Cellular Signals

“…Technologies such as confocal microscopy (21), synchrotron radiation computed tomography (22) and ultra-high-resolution computed tomography (23) have been applied ex vivo to attempt to capture the microstructural geometry. With these methods, several authors (22, 24) have performed comprehensive analyses of osteocyte networks and individual lacunae, assessing typical densities and distributions (22, 23), as well as studies on strain amplification on individual lacunae-canaliculi structures (21). Even with the multitude of tools and techniques available to gather information, they are often single-scale focused, and seem to struggle coupling the hierarchies of bone.…”

“…Cresswell et al (23, 29) applied a similar approach to calculate the mechanical in vivo environment during (re)modelling in rat vertebrae. Micro-CT images of rat vertebrae were converted to micro-FE appropriate hexahedral element using custom software and solved using ABAQUS (29) or a custom solver (23). Similarly, the SED, maximum principle strain and von Mises stress for each element represented the local mechanical in vivo environment.…”

Musculoskeletal mechanobiology: A new era for MechanoMedicine

“…This special issue begins with several outstanding reviews that provide updates on the significance of mechanobiology in musculoskeletal research involving cartilage, tendon, muscle and bone, [1][2][3][4][5][6][7][8][9][10] and that span topics from the role of candidate mechanosensors and chemical mediators, 1,5,9,10 in vitro and in vivo models of tissue injury and repair, 3,4 and supporting technologies. 6,7 The majority of original articles following the review papers are related to the mechanobiology of bone and cartilage, [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] tissues whose physical regulation have traditionally garnered intensive research focus, followed by complementary research papers in areas of growing prominence: Ligaments, intervertebral discs, and stem cells. [24][25][26][27][28] From this Special Issue in Musculoskeletal Mechanobiology, it is clear that it has become technically possible to trace the impact of mechanics from individual molecules to an entire organism.…”