Mechanosignaling in bone health, trauma and inflammation

Derrick M. Knapik, Priyangi Perera, Jin Nam, Alisa D. Blazek, Björn Rath, Binnaz Leblebicioglu, Hiranmoy Das, Lai Chu Wu, Timothy Hewett, Suresh K. Agarwal, Alexander G. Robling, David C. Flanigan, Beth S. Lee, Sudha Agarwal

Research output: Contribution to journalReview article

18 Citations (Scopus)

Abstract

Significance: Mechanosignaling is vital for maintaining the structural integrity of bone under physiologic conditions. These signals activate and suppress multiple signaling cascades regulating bone formation and resorption. Understanding these pathways is of prime importance to exploit their therapeutic potential in disorders associated with bone loss due to disuse, trauma, or disruption of homeostatic mechanisms. Recent Advances: In the case of cells of the bone, an impressive amount of data has been generated that provides evidence of a complex mechanism by which mechanical signals can maintain or disrupt cellular homeostasis by driving transcriptional regulation of growth factors, matrix proteins and inflammatory mediators in health and inflammation. Mechanical signals act on cells in a magnitude dependent manner to induce bone deposition or resorption. During health, physiological levels of these signals are essential for maintaining bone strength and architecture, whereas during inflammation, similar signals can curb inflammation by suppressing the nuclear factor kappa B (NF-κB) signaling cascade, while upregulating matrix synthesis via mothers against decapentaplegic homolog and/or Wnt signaling cascades. Contrarily, excessive mechanical forces can induce inflammation via activation of the NF-κB signaling cascade. Critical Issues: Given the osteogenic potential of mechanical signals, it is imperative to exploit their therapeutic efficacy for the treatment of bone disorders. Here we review select signaling pathways and mediators stimulated by mechanical signals to modulate the strength and integrity of the bone. Future Directions: Understanding the mechanisms of mechanotransduction and its effects on bone lay the groundwork for development of nonpharmacologic mechanostimulatory approaches for osteodegenerative diseases and optimal bone health. Antioxid. Redox Signal. 20, 970-985.

Original languageEnglish (US)
Pages (from-to)970-985
Number of pages16
JournalAntioxidants and Redox Signaling
Volume20
Issue number6
DOIs
StatePublished - Feb 20 2014
Externally publishedYes

Fingerprint

Bone
Health
Inflammation
Bone and Bones
Wounds and Injuries
NF-kappa B
Smad Proteins
Bone Diseases
Bone Resorption
Curbs
Osteogenesis
Oxidation-Reduction
Structural integrity
Intercellular Signaling Peptides and Proteins
Homeostasis
Chemical activation
Therapeutics
Proteins

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Physiology
  • Clinical Biochemistry

Cite this

Knapik, D. M., Perera, P., Nam, J., Blazek, A. D., Rath, B., Leblebicioglu, B., ... Agarwal, S. (2014). Mechanosignaling in bone health, trauma and inflammation. Antioxidants and Redox Signaling, 20(6), 970-985. https://doi.org/10.1089/ars.2013.5467

Mechanosignaling in bone health, trauma and inflammation. / Knapik, Derrick M.; Perera, Priyangi; Nam, Jin; Blazek, Alisa D.; Rath, Björn; Leblebicioglu, Binnaz; Das, Hiranmoy; Wu, Lai Chu; Hewett, Timothy; Agarwal, Suresh K.; Robling, Alexander G.; Flanigan, David C.; Lee, Beth S.; Agarwal, Sudha.

In: Antioxidants and Redox Signaling, Vol. 20, No. 6, 20.02.2014, p. 970-985.

Research output: Contribution to journalReview article

Knapik, DM, Perera, P, Nam, J, Blazek, AD, Rath, B, Leblebicioglu, B, Das, H, Wu, LC, Hewett, T, Agarwal, SK, Robling, AG, Flanigan, DC, Lee, BS & Agarwal, S 2014, 'Mechanosignaling in bone health, trauma and inflammation', Antioxidants and Redox Signaling, vol. 20, no. 6, pp. 970-985. https://doi.org/10.1089/ars.2013.5467
Knapik DM, Perera P, Nam J, Blazek AD, Rath B, Leblebicioglu B et al. Mechanosignaling in bone health, trauma and inflammation. Antioxidants and Redox Signaling. 2014 Feb 20;20(6):970-985. https://doi.org/10.1089/ars.2013.5467
Knapik, Derrick M. ; Perera, Priyangi ; Nam, Jin ; Blazek, Alisa D. ; Rath, Björn ; Leblebicioglu, Binnaz ; Das, Hiranmoy ; Wu, Lai Chu ; Hewett, Timothy ; Agarwal, Suresh K. ; Robling, Alexander G. ; Flanigan, David C. ; Lee, Beth S. ; Agarwal, Sudha. / Mechanosignaling in bone health, trauma and inflammation. In: Antioxidants and Redox Signaling. 2014 ; Vol. 20, No. 6. pp. 970-985.
@article{596bcf877f6c4039a778844f2eef72f4,
title = "Mechanosignaling in bone health, trauma and inflammation",
abstract = "Significance: Mechanosignaling is vital for maintaining the structural integrity of bone under physiologic conditions. These signals activate and suppress multiple signaling cascades regulating bone formation and resorption. Understanding these pathways is of prime importance to exploit their therapeutic potential in disorders associated with bone loss due to disuse, trauma, or disruption of homeostatic mechanisms. Recent Advances: In the case of cells of the bone, an impressive amount of data has been generated that provides evidence of a complex mechanism by which mechanical signals can maintain or disrupt cellular homeostasis by driving transcriptional regulation of growth factors, matrix proteins and inflammatory mediators in health and inflammation. Mechanical signals act on cells in a magnitude dependent manner to induce bone deposition or resorption. During health, physiological levels of these signals are essential for maintaining bone strength and architecture, whereas during inflammation, similar signals can curb inflammation by suppressing the nuclear factor kappa B (NF-κB) signaling cascade, while upregulating matrix synthesis via mothers against decapentaplegic homolog and/or Wnt signaling cascades. Contrarily, excessive mechanical forces can induce inflammation via activation of the NF-κB signaling cascade. Critical Issues: Given the osteogenic potential of mechanical signals, it is imperative to exploit their therapeutic efficacy for the treatment of bone disorders. Here we review select signaling pathways and mediators stimulated by mechanical signals to modulate the strength and integrity of the bone. Future Directions: Understanding the mechanisms of mechanotransduction and its effects on bone lay the groundwork for development of nonpharmacologic mechanostimulatory approaches for osteodegenerative diseases and optimal bone health. Antioxid. Redox Signal. 20, 970-985.",
author = "Knapik, {Derrick M.} and Priyangi Perera and Jin Nam and Blazek, {Alisa D.} and Bj{\"o}rn Rath and Binnaz Leblebicioglu and Hiranmoy Das and Wu, {Lai Chu} and Timothy Hewett and Agarwal, {Suresh K.} and Robling, {Alexander G.} and Flanigan, {David C.} and Lee, {Beth S.} and Sudha Agarwal",
year = "2014",
month = "2",
day = "20",
doi = "10.1089/ars.2013.5467",
language = "English (US)",
volume = "20",
pages = "970--985",
journal = "Antioxidants and Redox Signaling",
issn = "1523-0864",
publisher = "Mary Ann Liebert Inc.",
number = "6",

}

TY - JOUR

T1 - Mechanosignaling in bone health, trauma and inflammation

AU - Knapik, Derrick M.

AU - Perera, Priyangi

AU - Nam, Jin

AU - Blazek, Alisa D.

AU - Rath, Björn

AU - Leblebicioglu, Binnaz

AU - Das, Hiranmoy

AU - Wu, Lai Chu

AU - Hewett, Timothy

AU - Agarwal, Suresh K.

AU - Robling, Alexander G.

AU - Flanigan, David C.

AU - Lee, Beth S.

AU - Agarwal, Sudha

PY - 2014/2/20

Y1 - 2014/2/20

N2 - Significance: Mechanosignaling is vital for maintaining the structural integrity of bone under physiologic conditions. These signals activate and suppress multiple signaling cascades regulating bone formation and resorption. Understanding these pathways is of prime importance to exploit their therapeutic potential in disorders associated with bone loss due to disuse, trauma, or disruption of homeostatic mechanisms. Recent Advances: In the case of cells of the bone, an impressive amount of data has been generated that provides evidence of a complex mechanism by which mechanical signals can maintain or disrupt cellular homeostasis by driving transcriptional regulation of growth factors, matrix proteins and inflammatory mediators in health and inflammation. Mechanical signals act on cells in a magnitude dependent manner to induce bone deposition or resorption. During health, physiological levels of these signals are essential for maintaining bone strength and architecture, whereas during inflammation, similar signals can curb inflammation by suppressing the nuclear factor kappa B (NF-κB) signaling cascade, while upregulating matrix synthesis via mothers against decapentaplegic homolog and/or Wnt signaling cascades. Contrarily, excessive mechanical forces can induce inflammation via activation of the NF-κB signaling cascade. Critical Issues: Given the osteogenic potential of mechanical signals, it is imperative to exploit their therapeutic efficacy for the treatment of bone disorders. Here we review select signaling pathways and mediators stimulated by mechanical signals to modulate the strength and integrity of the bone. Future Directions: Understanding the mechanisms of mechanotransduction and its effects on bone lay the groundwork for development of nonpharmacologic mechanostimulatory approaches for osteodegenerative diseases and optimal bone health. Antioxid. Redox Signal. 20, 970-985.

AB - Significance: Mechanosignaling is vital for maintaining the structural integrity of bone under physiologic conditions. These signals activate and suppress multiple signaling cascades regulating bone formation and resorption. Understanding these pathways is of prime importance to exploit their therapeutic potential in disorders associated with bone loss due to disuse, trauma, or disruption of homeostatic mechanisms. Recent Advances: In the case of cells of the bone, an impressive amount of data has been generated that provides evidence of a complex mechanism by which mechanical signals can maintain or disrupt cellular homeostasis by driving transcriptional regulation of growth factors, matrix proteins and inflammatory mediators in health and inflammation. Mechanical signals act on cells in a magnitude dependent manner to induce bone deposition or resorption. During health, physiological levels of these signals are essential for maintaining bone strength and architecture, whereas during inflammation, similar signals can curb inflammation by suppressing the nuclear factor kappa B (NF-κB) signaling cascade, while upregulating matrix synthesis via mothers against decapentaplegic homolog and/or Wnt signaling cascades. Contrarily, excessive mechanical forces can induce inflammation via activation of the NF-κB signaling cascade. Critical Issues: Given the osteogenic potential of mechanical signals, it is imperative to exploit their therapeutic efficacy for the treatment of bone disorders. Here we review select signaling pathways and mediators stimulated by mechanical signals to modulate the strength and integrity of the bone. Future Directions: Understanding the mechanisms of mechanotransduction and its effects on bone lay the groundwork for development of nonpharmacologic mechanostimulatory approaches for osteodegenerative diseases and optimal bone health. Antioxid. Redox Signal. 20, 970-985.

UR - http://www.scopus.com/inward/record.url?scp=84893826138&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84893826138&partnerID=8YFLogxK

U2 - 10.1089/ars.2013.5467

DO - 10.1089/ars.2013.5467

M3 - Review article

VL - 20

SP - 970

EP - 985

JO - Antioxidants and Redox Signaling

JF - Antioxidants and Redox Signaling

SN - 1523-0864

IS - 6

ER -