Bone Geometry Is Altered by Follistatin‐Induced Muscle Growth in Young Adult Male Mice

Chan, Audrey S.; McGregor, Narelle E; Poulton, Ingrid J; Hardee, Justin P.; Cho, Hyun Jung; Martın, Thomas; Gregorevic, Paul; Sims, Natalie A.; Lynch, Gordon S.

doi:10.1002/jbm4.10477

Cited by 8 publications

(10 citation statements)

References 83 publications

(143 reference statements)

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“…Image in panel A is taken from http://www.informatics.jax.org/cookbook/figures/figure42.shtml. 6. Calculate the length of the metaphyseal region of interest (ROI) for each sample based on the bone length.…”

Section: Materials and Reagentsmentioning

confidence: 99%

Measuring Bone Volume at Multiple Densities by Micro-computed Tomography

Walker¹,

McGregor²,

Chan³

et al. 2021

BIO-PROTOCOL

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Bone strength is controlled by both bone mass, and the organization and quality of the bone material. The current standard method for measuring bone mass in mouse and rat studies is micro-computed tomography. This method typically uses a single threshold to identify bone material in the cortical and trabecular regions. However, this single threshold method obscures information about the mineral content of the bone material and depends on normal morphology to separately analyze cortical and trabecular structures. To extend this method to identify bone mass at multiple density levels, we have established a protocol for unbiased selection and application of multiple thresholds using a standard laboratory-based micro-computed tomography instrument. This non-invasive method can be applied to longitudinal studies and archived samples and provides additional information about bone structure and strength.

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Section: Materials and Reagentsmentioning

confidence: 99%

Measuring Bone Volume at Multiple Densities by Micro-computed Tomography

Walker¹,

McGregor²,

Chan³

et al. 2021

BIO-PROTOCOL

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“…Because the effect of tibial loading varies around the circumference of the bone, (34)(35)(36) and standard micro-CT measurements calculate an average cortical thickness, we next assessed cortical thickness radially around the bone, as previously described, (20) and calculated the difference between loaded and non-loaded limbs of the same animals at the same anatomical sites (difference shown in Fig. 4A; data for each limb are shown separately in Supplemental Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Such a mechanism is consistent with our observations of less high density bone in the bones from exercised Dmp1Cre.Socs3 f/f mice, and suggests that local bone demineralization may be exaggerated in response to treadmill running in these mice. Whether this effect is due to direct effects of exercise-induced load, to local or systemic actions of STAT3-signaling myokines (such as CNTF, IL-6, and OSM) released from exercising muscle, (53,54) or from altered muscle-derived strains or changes in muscle size (20) is not yet clear. Most importantly, even though the skeletal impacts of tibial loading and treadmill running are different, both are exaggerated in Dmp1Cre.Socs3 f/f bones.…”

Section: Discussionmentioning

confidence: 99%

“…To determine the difference in effect between genotypes at the same anatomical location in the loading study, cortical thickness was measured around the central axis of the tibia, using a previously described method. (20) This used a custom script written in ImageJ macro using FIJI software. In each cross-sectional image, a Euclidean distance map (EDM) image was generated from the inner boundary of the bone.…”

Section: Micro-ct Scanning and Analysesmentioning

confidence: 99%

“…(17,18) Mechanical forces, including those exerted by skeletal muscles, influence all stages of skeletal development, from embryogenesis (19) through to later influences on bone shape in the young adult. (20) We recently described a mouse model with increased STAT3 phosphorylation in osteocytes and delayed postnatal cortical consolidation. (21,22) In this model, the Dmp1Cre.Socs3 f/f mouse, STAT3 phosphorylation in cortical osteocytes is constitutively greater than in control mice, and the STAT3 phosphorylation response of calvarial osteocytes to IL-6 family cytokine treatment is elevated and prolonged.…”

Section: Introductionmentioning

confidence: 99%

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STAT3 Hyperactivation Due to SOCS3 Deletion in Murine Osteocytes Accentuates Responses to Exercise- and Load-Induced Bone Formation

McGregor

Walker

Chan

et al. 2020

Journal of Bone and Mineral Research

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Cortical bone develops and changes in response to mechanical load, which is sensed by bone-embedded osteocytes. The bone formation response to load depends on STAT3 intracellular signals, which are upregulated after loading and are subject to negative feedback from Suppressor of Cytokine Signaling 3 (Socs3). Mice with Dmp1Cre-targeted knockout of Socs3 have elevated STAT3 signaling in osteocytes and display delayed cortical bone maturation characterized by impaired accrual of high-density lamellar bone. This study aimed to determine whether these mice exhibit an altered response to mechanical load. The approach used was to test both treadmill running and tibial compression in female Dmp1Cre.Socs3 f/f mice. Treadmill running for 5 days per week from 6 to 11 weeks of age did not change cortical bone mass in control mice, but further delayed cortical bone maturation in Dmp1Cre. Socs3 f/f mice; accrual of high-density bone was suppressed, and cortical thickness was less than in genetically-matched sedentary controls. When strain-matched anabolic tibial loading was tested, both control and Dmp1Cre.Socs3 f/f mice exhibited a significantly greater cortical thickness and periosteal perimeter in loaded tibia compared with the contralateral non-loaded bone. At the site of greatest compressive strain, the loaded Dmp1Cre.Socs3 f/f tibias showed a significantly greater response than controls, indicated by a greater increase in cortical thickness. This was due to a greater bone formation response on both periosteal and endocortical surfaces, including formation of abundant woven bone on the periosteum. This suggests a greater sensitivity to mechanical load in Dmp1Cre.Socs3 f/f bone. In summary, mice with targeted SOCS3 deletion and immature cortical bone have an exaggerated response to both physiological and experimental mechanical loads. We conclude that there is an optimal level of osteocytic response to mechanical load required for cortical bone maturation and that load-induced bone formation may be increased by augmenting STAT3 signaling within osteocytes.

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Cortical bone development, maintenance and porosity: genetic alterations in humans and mice influencing chondrocytes, osteoclasts, osteoblasts and osteocytes

Isojima

Sims

2021

Cell. Mol. Life Sci.

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Bone Geometry Is Altered by Follistatin‐Induced Muscle Growth in Young Adult Male Mice

Abstract: This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process which may lead to differences between this version and the Version of Record. Please cite this article as

Cited by 8 publications

References 83 publications

Measuring Bone Volume at Multiple Densities by Micro-computed Tomography

Measuring Bone Volume at Multiple Densities by Micro-computed Tomography

STAT3 Hyperactivation Due to SOCS3 Deletion in Murine Osteocytes Accentuates Responses to Exercise- and Load-Induced Bone Formation

Cortical bone development, maintenance and porosity: genetic alterations in humans and mice influencing chondrocytes, osteoclasts, osteoblasts and osteocytes

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