Gene expression of intracortical bone demonstrates loading-induced increases in Wnt1 and Ngf and inhibition of bone remodeling processes

Harris, Taylor L.; Silva, Matthew J.

doi:10.1016/j.bone.2021.116019

Cited by 10 publications

(23 citation statements)

References 85 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Gene expression analysis was performed 4-hr after the 5 th bout of loading. Congruent with previous reports [11][12] , we found that loading potently induced Wnt1 expression in the bone (Fig 6A). RT-qPCR analysis indicated that Wnt1 expression was 6.6-fold higher in the loaded vs non-loaded tibias of Wnt1F/F controls (p<0.0001).…”

Section: Induction Of Osteogenic Genes Was Diminished In the Bones Of...supporting

confidence: 89%

“…Tibial loading induces Wnt1 expression in bone (Kelly et al, 2016; Holguin et al, 2016; Harris and Silva, 2021). To identify the source of Wnt1 in response to loading, in situ hybridization was used to evaluate Wnt1 RNA expression in the loaded and non-loaded tibias of Wnt1 F/F control mice after 5 days of loading (Fig 1A).…”

Section: Resultsmentioning

confidence: 99%

“…Transcriptional profiling studies from our lab and others have identified Wnt1 as a mechano-responsive gene (Kelly et al 2016; Chermside-Scabbo et al 2020; Harris and Silva, 2021). RNASeq libraries prepared from the bones of 10 week old mice subjected to a single bout of loading showed that Wnt1 was highly enriched in the loaded vs non-loaded tibias 3 and 24-hrs after loading (Kelly, et al).…”

Section: Discussionmentioning

confidence: 96%

“…A single bout of loading in 5-month old mice increased Wnt1 expression in the tibia by nearly 6-fold (Chermside-Scabbo, et al 2020). Using laser capture microscopy, Harris et al isolated osteocyte vs osteoblast-enriched populations from the loaded and non-loaded bones of wild-type mice and found that Wnt1 was highly enriched in loaded bones, particularly in samples that were enriched for osteocytes (Harris, et al 2021).…”

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

Loading-Induced Bone Formation is Mediated by Wnt1 Induction in Osteoblast-Lineage Cells

Lawson

Migotsky

Chermside‐Scabbo

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

Mechanical loading on the skeleton stimulates bone formation. Although the exact mechanism underlying this process remains unknown, a growing body of evidence indicates that the Wnt signaling pathway is necessary for the skeletal response to loading. Recently, we showed that Wnts produced by osteoblast lineage cells mediate the osteo-anabolic response to tibial loading in adult mice. Here, we report that Wnt1 specifically plays a crucial role in mediating the mechano-adaptive response to loading. Independent of loading, short-term loss of Wnt1 in the Osx-lineage resulted in decreased cortical bone area in the tibias of 5-month old mice. In females, strain-matched loading enhanced periosteal bone formation in Wnt1F/F controls, but not in Wnt1F/F; OsxCreERT2 knockouts. In males, strain-matched loading increased periosteal bone formation in both control and knockout mice; however, the periosteal relative bone formation rate was 65% lower in Wnt1 knockouts versus controls. Together, these findings show that Wnt1 supports adult bone homeostasis and mediates the bone anabolic response to mechanical loading.

show abstract

Section: Induction Of Osteogenic Genes Was Diminished In the Bones Of...supporting

confidence: 89%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Loading-Induced Bone Formation is Mediated by Wnt1 Induction in Osteoblast-Lineage Cells

Lawson

Migotsky

Chermside‐Scabbo

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Microarray investigations reveal that mechanical loading promotes osteocytic gene expression of in situ osteocytes harvested from murine intracortical bone using laser capture microdissection approach. This biophysical manipulation also changes hundreds of gene transcription related to various metabolic activities [ 89 ].…”

Section: The Effects Of Biophysical Stimulation On Mitochondrial Functionmentioning

confidence: 99%

Biophysical Modulation of the Mitochondrial Metabolism and Redox in Bone Homeostasis and Osteoporosis: How Biophysics Converts into Bioenergetics

Wang

Chen

et al. 2021

Antioxidants

View full text Add to dashboard Cite

Bone-forming cells build mineralized microstructure and couple with bone-resorbing cells, harmonizing bone mineral acquisition, and remodeling to maintain bone mass homeostasis. Mitochondrial glycolysis and oxidative phosphorylation pathways together with ROS generation meet the energy requirement for bone-forming cell growth and differentiation, respectively. Moderate mechanical stimulations, such as weight loading, physical activity, ultrasound, vibration, and electromagnetic field stimulation, etc., are advantageous to bone-forming cell activity, promoting bone anabolism to compromise osteoporosis development. A plethora of molecules, including ion channels, integrins, focal adhesion kinases, and myokines, are mechanosensitive and transduce mechanical stimuli into intercellular signaling, regulating growth, mineralized extracellular matrix biosynthesis, and resorption. Mechanical stimulation changes mitochondrial respiration, biogenesis, dynamics, calcium influx, and redox, whereas mechanical disuse induces mitochondrial dysfunction and oxidative stress, which aggravates bone-forming cell apoptosis, senescence, and dysfunction. The control of the mitochondrial biogenesis activator PGC-1α by NAD+-dependent deacetylase sirtuins or myokine FNDC/irisin or repression of oxidative stress by mitochondrial antioxidant Nrf2 modulates the biophysical stimulation for the promotion of bone integrity. This review sheds light onto the roles of mechanosensitive signaling, mitochondrial dynamics, and antioxidants in mediating the anabolic effects of biophysical stimulation to bone tissue and highlights the remedial potential of mitochondrial biogenesis regulators for osteoporosis.

show abstract

Osteocyte Estrogen Receptor β (Ot-ERβ) Regulates Bone Turnover and Skeletal Adaptive Response to Mechanical Loading Differently in Male and Female Growing and Adult Mice

Yang

Bullock

et al. 2020

Journal of Bone and Mineral Research

View full text Add to dashboard Cite

Age‐related bone loss is a failure of balanced bone turnover and diminished skeletal mechanoadaptation. Estrogen receptors, ERα and ERβ, play critical roles in osteoprotective regulation activated by estrogen and mechanical signals. Previous studies mainly focused on ERα and showed that osteocyte‐ERα (Ot‐ERα) regulated trabecular, but not cortical bone, and played a minor role in load‐induced cortical adaptation. However, the role of Ot‐ERβ in bone mass regulation remains unrevealed. To address this issue, we characterized bone (re)modeling and gene expression in male and female mice with Ot‐ERβ deletion (ERβ‐dOT) and littermate control (LC) at 10 weeks (young) or 28 weeks (adult) of age, as well as their responses to in vivo tibial compressive loading. Increased cancellous bone mass appeared in the L4 vertebral body of young male ERβ‐dOT mice. At the same time, femoral cortical bone gene expression showed signs consistent with elevated osteoblast and osteoclast activities (type‐I collagen, Cat K, RANKL). Upregulated androgen receptor (AR) expression was observed in young male ERβ‐dOT mice relative to LC, suggesting a compensatory effect of testosterone on male bone protection. In contrast, bone mass in L4 decreased in adult male ERβ‐dOT mice, attributed to potentially increased bone resorption activity (Cat K) with no change in bone formation. There was no effect of ERβ‐dOT on bone mass or gene expression in female mice. Sex‐dependent regulation of Ot‐ERβ also appeared in load‐induced cortical responsiveness. Young female ERβ‐dOT mice showed an enhanced tibial cortical anabolic adaptation compared with LC. In contrast, an attenuated cortical anabolic response presented at the proximal tibia in male ERβ‐dOT mice at both ages. For the first time, our findings suggest that Ot‐ERβ regulates bone (re)modeling and the response to mechanical signals through different mechanisms in males and females. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

show abstract

Gene expression of intracortical bone demonstrates loading-induced increases in Wnt1 and Ngf and inhibition of bone remodeling processes

Cited by 10 publications

References 85 publications

Loading-Induced Bone Formation is Mediated by Wnt1 Induction in Osteoblast-Lineage Cells

Loading-Induced Bone Formation is Mediated by Wnt1 Induction in Osteoblast-Lineage Cells

Biophysical Modulation of the Mitochondrial Metabolism and Redox in Bone Homeostasis and Osteoporosis: How Biophysics Converts into Bioenergetics

Osteocyte Estrogen Receptor β (Ot-ERβ) Regulates Bone Turnover and Skeletal Adaptive Response to Mechanical Loading Differently in Male and Female Growing and Adult Mice

Contact Info

Product

Resources

About