Advanced

Reduced expression of BMP-3 due to mechanical loading: a link between mechanical stimuli and tissue differentiation

Aspenberg, Per LU ; Basic, N; Tägil, Magnus LU and Vukicevic, S (2000) In Acta Orthopaedica Scandinavica 71(6). p.558-562
Abstract
Mechanical signaling and BMP expression appear to be involved in controlling the differentiation of cartilage in fracture repair, but the connection between mechanics and BMP signaling is not known. In this study of rats, we used a bone chamber to see how BMP gene expression was changed by a mechanical loading regime that induces cartilage formation in this model. We compared the still undifferentiated tissue in loaded and unloaded chambers in the same rat regarding the expression of TGFbeta-1, BMP-2, 3, 4, 5, 6, 7, CDMP-1, 2 and ALK-2 and 3 by using RT-PCR normalized against GAPDH. We found expression of TGFbeta-1, BMP-2 and 4 in all specimens, and BMP 5-7 and CDMPs in none. 1 week after loading started, BMP-3 was strongly expressed in... (More)
Mechanical signaling and BMP expression appear to be involved in controlling the differentiation of cartilage in fracture repair, but the connection between mechanics and BMP signaling is not known. In this study of rats, we used a bone chamber to see how BMP gene expression was changed by a mechanical loading regime that induces cartilage formation in this model. We compared the still undifferentiated tissue in loaded and unloaded chambers in the same rat regarding the expression of TGFbeta-1, BMP-2, 3, 4, 5, 6, 7, CDMP-1, 2 and ALK-2 and 3 by using RT-PCR normalized against GAPDH. We found expression of TGFbeta-1, BMP-2 and 4 in all specimens, and BMP 5-7 and CDMPs in none. 1 week after loading started, BMP-3 was strongly expressed in the unloaded control specimens in 7 of 8 animals, but detectable in only I of the contralateral loaded ones. After 2 weeks of loading, the BMP-3 expression pattern was less clear, but with both time groups taken together, there was still less BMP-3 expression on the loaded side in 9 rats, more in 1 and no difference in 5 (p = 0.01). ALK-2 at 1 week was expressed in all specimens expressing BMP-3 and in none of the others. At 2 weeks, ALK-2 was expressed in all specimens. Thus, a loading regime, known to induce cartilage in this model, caused down-regulation of BMP-3 and ALK-2. The results are consistent with the view that BMP-3 inhibits differentiation, as recently described. This role appears to be linked to the ALK-2 receptor. Most importantly, the results indicate a link between mechanical signaling and BMP expression such that mechanically-induced down-regulation of the inhibiting BMP-3 enabled the induction of cartilage. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Acta Orthopaedica Scandinavica
volume
71
issue
6
pages
558 - 562
publisher
Taylor & Francis
external identifiers
  • pmid:11145381
  • scopus:0033674978
ISSN
0001-6470
DOI
10.1080/000164700317362172
language
English
LU publication?
yes
id
93365190-b277-43b3-963b-300aedd7a1be (old id 1117281)
date added to LUP
2008-07-01 08:37:39
date last changed
2017-01-01 07:01:37
@article{93365190-b277-43b3-963b-300aedd7a1be,
  abstract     = {Mechanical signaling and BMP expression appear to be involved in controlling the differentiation of cartilage in fracture repair, but the connection between mechanics and BMP signaling is not known. In this study of rats, we used a bone chamber to see how BMP gene expression was changed by a mechanical loading regime that induces cartilage formation in this model. We compared the still undifferentiated tissue in loaded and unloaded chambers in the same rat regarding the expression of TGFbeta-1, BMP-2, 3, 4, 5, 6, 7, CDMP-1, 2 and ALK-2 and 3 by using RT-PCR normalized against GAPDH. We found expression of TGFbeta-1, BMP-2 and 4 in all specimens, and BMP 5-7 and CDMPs in none. 1 week after loading started, BMP-3 was strongly expressed in the unloaded control specimens in 7 of 8 animals, but detectable in only I of the contralateral loaded ones. After 2 weeks of loading, the BMP-3 expression pattern was less clear, but with both time groups taken together, there was still less BMP-3 expression on the loaded side in 9 rats, more in 1 and no difference in 5 (p = 0.01). ALK-2 at 1 week was expressed in all specimens expressing BMP-3 and in none of the others. At 2 weeks, ALK-2 was expressed in all specimens. Thus, a loading regime, known to induce cartilage in this model, caused down-regulation of BMP-3 and ALK-2. The results are consistent with the view that BMP-3 inhibits differentiation, as recently described. This role appears to be linked to the ALK-2 receptor. Most importantly, the results indicate a link between mechanical signaling and BMP expression such that mechanically-induced down-regulation of the inhibiting BMP-3 enabled the induction of cartilage.},
  author       = {Aspenberg, Per and Basic, N and Tägil, Magnus and Vukicevic, S},
  issn         = {0001-6470},
  language     = {eng},
  number       = {6},
  pages        = {558--562},
  publisher    = {Taylor & Francis},
  series       = {Acta Orthopaedica Scandinavica},
  title        = {Reduced expression of BMP-3 due to mechanical loading: a link between mechanical stimuli and tissue differentiation},
  url          = {http://dx.doi.org/10.1080/000164700317362172},
  volume       = {71},
  year         = {2000},
}