Absence of Cx43 selectively from osteocytes enhances responsiveness to mechanical force in mice

Nicoletta Bivi, Rafael Pacheco-Costa, Lucas R. Brun, Thomas R. Murphy, Nathan R. Farlow, Alexander G. Robling, Teresita Bellido, Lilian I. Plotkin

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

The osteocyte network is crucial for the response of bone to mechanical force. Within this network, connexin43 (Cx43) is thought to mediate the communication of osteocytes and osteoblasts among themselves and the exchange of small molecules with the extracellular milieu. Despite recent advances in understanding Cx43 role for the response of bone cells to mechanical stimulation, the contribution of Cx43 specifically in osteocytes to mechanotransduction in vivo is not well-known. We examined the anabolic response to ulnar axial loading of mice lacking Cx43 in osteocytes (Cx43 ΔOt). Loading induced a greater increase in periosteal bone formation rate in Cx43ΔOt mice compared to control littermates, resulting from higher mineralizing surface and enhanced mineral apposition rate. Expression of β-catenin protein, a molecule implicated in mechanotransduction, was higher in bones from Cx43ΔOt mice, compared to littermate controls. In addition, MLO-Y4 osteocytic cells knocked-down for Cx43 exhibited higher β-catenin protein expression and enhanced response to mechanical stimulation. These findings suggest that osteocytes lacking Cx43 are "primed" to respond to mechanical stimulation and that absence of Cx43 in osteocytes unleashes bone formation, by a mechanism that might involve accumulation of β-catenin.

Original languageEnglish (US)
Pages (from-to)1075-1081
Number of pages7
JournalJournal of Orthopaedic Research
Volume31
Issue number7
DOIs
StatePublished - Jul 1 2013

Fingerprint

Osteocytes
Connexin 43
Catenins
Osteogenesis
Bone and Bones
Weight-Bearing
Osteoblasts
Minerals
Communication

Keywords

  • β-catenin
  • bone formation
  • connexin43
  • mechanical loading
  • osteocyte

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine

Cite this

Absence of Cx43 selectively from osteocytes enhances responsiveness to mechanical force in mice. / Bivi, Nicoletta; Pacheco-Costa, Rafael; Brun, Lucas R.; Murphy, Thomas R.; Farlow, Nathan R.; Robling, Alexander G.; Bellido, Teresita; Plotkin, Lilian I.

In: Journal of Orthopaedic Research, Vol. 31, No. 7, 01.07.2013, p. 1075-1081.

Research output: Contribution to journalArticle

Bivi, Nicoletta ; Pacheco-Costa, Rafael ; Brun, Lucas R. ; Murphy, Thomas R. ; Farlow, Nathan R. ; Robling, Alexander G. ; Bellido, Teresita ; Plotkin, Lilian I. / Absence of Cx43 selectively from osteocytes enhances responsiveness to mechanical force in mice. In: Journal of Orthopaedic Research. 2013 ; Vol. 31, No. 7. pp. 1075-1081.
@article{03243e8ed95a46068f62cb54f8bf491f,
title = "Absence of Cx43 selectively from osteocytes enhances responsiveness to mechanical force in mice",
abstract = "The osteocyte network is crucial for the response of bone to mechanical force. Within this network, connexin43 (Cx43) is thought to mediate the communication of osteocytes and osteoblasts among themselves and the exchange of small molecules with the extracellular milieu. Despite recent advances in understanding Cx43 role for the response of bone cells to mechanical stimulation, the contribution of Cx43 specifically in osteocytes to mechanotransduction in vivo is not well-known. We examined the anabolic response to ulnar axial loading of mice lacking Cx43 in osteocytes (Cx43 ΔOt). Loading induced a greater increase in periosteal bone formation rate in Cx43ΔOt mice compared to control littermates, resulting from higher mineralizing surface and enhanced mineral apposition rate. Expression of β-catenin protein, a molecule implicated in mechanotransduction, was higher in bones from Cx43ΔOt mice, compared to littermate controls. In addition, MLO-Y4 osteocytic cells knocked-down for Cx43 exhibited higher β-catenin protein expression and enhanced response to mechanical stimulation. These findings suggest that osteocytes lacking Cx43 are {"}primed{"} to respond to mechanical stimulation and that absence of Cx43 in osteocytes unleashes bone formation, by a mechanism that might involve accumulation of β-catenin.",
keywords = "β-catenin, bone formation, connexin43, mechanical loading, osteocyte",
author = "Nicoletta Bivi and Rafael Pacheco-Costa and Brun, {Lucas R.} and Murphy, {Thomas R.} and Farlow, {Nathan R.} and Robling, {Alexander G.} and Teresita Bellido and Plotkin, {Lilian I.}",
year = "2013",
month = "7",
day = "1",
doi = "10.1002/jor.22341",
language = "English (US)",
volume = "31",
pages = "1075--1081",
journal = "Journal of Orthopaedic Research",
issn = "0736-0266",
publisher = "John Wiley and Sons Inc.",
number = "7",

}

TY - JOUR

T1 - Absence of Cx43 selectively from osteocytes enhances responsiveness to mechanical force in mice

AU - Bivi, Nicoletta

AU - Pacheco-Costa, Rafael

AU - Brun, Lucas R.

AU - Murphy, Thomas R.

AU - Farlow, Nathan R.

AU - Robling, Alexander G.

AU - Bellido, Teresita

AU - Plotkin, Lilian I.

PY - 2013/7/1

Y1 - 2013/7/1

N2 - The osteocyte network is crucial for the response of bone to mechanical force. Within this network, connexin43 (Cx43) is thought to mediate the communication of osteocytes and osteoblasts among themselves and the exchange of small molecules with the extracellular milieu. Despite recent advances in understanding Cx43 role for the response of bone cells to mechanical stimulation, the contribution of Cx43 specifically in osteocytes to mechanotransduction in vivo is not well-known. We examined the anabolic response to ulnar axial loading of mice lacking Cx43 in osteocytes (Cx43 ΔOt). Loading induced a greater increase in periosteal bone formation rate in Cx43ΔOt mice compared to control littermates, resulting from higher mineralizing surface and enhanced mineral apposition rate. Expression of β-catenin protein, a molecule implicated in mechanotransduction, was higher in bones from Cx43ΔOt mice, compared to littermate controls. In addition, MLO-Y4 osteocytic cells knocked-down for Cx43 exhibited higher β-catenin protein expression and enhanced response to mechanical stimulation. These findings suggest that osteocytes lacking Cx43 are "primed" to respond to mechanical stimulation and that absence of Cx43 in osteocytes unleashes bone formation, by a mechanism that might involve accumulation of β-catenin.

AB - The osteocyte network is crucial for the response of bone to mechanical force. Within this network, connexin43 (Cx43) is thought to mediate the communication of osteocytes and osteoblasts among themselves and the exchange of small molecules with the extracellular milieu. Despite recent advances in understanding Cx43 role for the response of bone cells to mechanical stimulation, the contribution of Cx43 specifically in osteocytes to mechanotransduction in vivo is not well-known. We examined the anabolic response to ulnar axial loading of mice lacking Cx43 in osteocytes (Cx43 ΔOt). Loading induced a greater increase in periosteal bone formation rate in Cx43ΔOt mice compared to control littermates, resulting from higher mineralizing surface and enhanced mineral apposition rate. Expression of β-catenin protein, a molecule implicated in mechanotransduction, was higher in bones from Cx43ΔOt mice, compared to littermate controls. In addition, MLO-Y4 osteocytic cells knocked-down for Cx43 exhibited higher β-catenin protein expression and enhanced response to mechanical stimulation. These findings suggest that osteocytes lacking Cx43 are "primed" to respond to mechanical stimulation and that absence of Cx43 in osteocytes unleashes bone formation, by a mechanism that might involve accumulation of β-catenin.

KW - β-catenin

KW - bone formation

KW - connexin43

KW - mechanical loading

KW - osteocyte

UR - http://www.scopus.com/inward/record.url?scp=84878204226&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84878204226&partnerID=8YFLogxK

U2 - 10.1002/jor.22341

DO - 10.1002/jor.22341

M3 - Article

C2 - 23483620

AN - SCOPUS:84878204226

VL - 31

SP - 1075

EP - 1081

JO - Journal of Orthopaedic Research

JF - Journal of Orthopaedic Research

SN - 0736-0266

IS - 7

ER -