Mechanical loading stimulates BMP7, but not BMP2, production by osteocytes

Ana Santos, Astrid D. Bakker, Hubertine Willems, Nathalie Bravenboer, Antonius L.J.J. Bronckers, Jenneke Klein-Nulend

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Bone mechanical adaptation is a cellular process that allows bones to adapt their mass and structure to mechanical loading. This process is governed by the osteocytes, which in response to mechanical loading produce signaling molecules that affect osteoblasts and osteoclasts. Bone morphogenic proteins (BMPs) are excellent candidates as signaling molecules, but it is unknown whether mechanically stimulated osteocytes affect bone adaptation through BMP production. Therefore, the aim of this study was to assess whether osteocytes produce BMPs in response to mechanical loading. In addition, since BMP7 has a vitamin D receptor (VDR) response element in the promoter region, we also investigated whether VDR is involved in the BMP7 response to mechanical loading. Human or VDR -/- mouse primary bone cells were submitted in vitro to 1 h pulsating fluid flow (PFF) and postincubated without PFF (PI) for 1-24 h, and gene and protein expression of BMP2 and BMP7 were quantified. In human bone cells, PFF did not change BMP2 gene expression, but it upregulated BMP7 gene expression by 4.4- to 5.6-fold at 1-3 h PI and stimulated BMP7 protein expression by 2.4-fold at 6 h PI. PFF did not stimulate BMP7 gene expression in VDR -/- mouse bone cells. These results show for the first time that mechanical loading upregulates BMP7, likely via the VDR, but not BMP2, gene and protein expression in osteocytes in vitro. Since BMP7 plays a major role in bone development and remodeling, these data might contribute to a better understanding of the mechanism leading to the mechanical adaptation of bone.

Original languageEnglish (US)
Pages (from-to)318-326
Number of pages9
JournalCalcified Tissue International
Volume89
Issue number4
DOIs
StatePublished - Oct 1 2011

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Osteocytes
Bone and Bones
Calcitriol Receptors
Pulsatile Flow
Gene Expression
Proteins
Vitamin D Response Element
Bone Remodeling
Bone Development
Osteoclasts
Osteoblasts
Genetic Promoter Regions
Up-Regulation

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine
  • Endocrinology

Cite this

Santos, A., Bakker, A. D., Willems, H., Bravenboer, N., Bronckers, A. L. J. J., & Klein-Nulend, J. (2011). Mechanical loading stimulates BMP7, but not BMP2, production by osteocytes. Calcified Tissue International, 89(4), 318-326. https://doi.org/10.1007/s00223-011-9521-1

Mechanical loading stimulates BMP7, but not BMP2, production by osteocytes. / Santos, Ana; Bakker, Astrid D.; Willems, Hubertine; Bravenboer, Nathalie; Bronckers, Antonius L.J.J.; Klein-Nulend, Jenneke.

In: Calcified Tissue International, Vol. 89, No. 4, 01.10.2011, p. 318-326.

Research output: Contribution to journalArticle

Santos, A, Bakker, AD, Willems, H, Bravenboer, N, Bronckers, ALJJ & Klein-Nulend, J 2011, 'Mechanical loading stimulates BMP7, but not BMP2, production by osteocytes', Calcified Tissue International, vol. 89, no. 4, pp. 318-326. https://doi.org/10.1007/s00223-011-9521-1
Santos, Ana ; Bakker, Astrid D. ; Willems, Hubertine ; Bravenboer, Nathalie ; Bronckers, Antonius L.J.J. ; Klein-Nulend, Jenneke. / Mechanical loading stimulates BMP7, but not BMP2, production by osteocytes. In: Calcified Tissue International. 2011 ; Vol. 89, No. 4. pp. 318-326.
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