Fibroblasts from mice with progessive ankylosis proliferate excessively in response to transforming growth factor-beta 1.

Abstract

BACKGROUND:

Murine progressive ankylosis (MPA) is a spontaneous arthropathy that produces ankylosis of peripheral and spinal joints in mice homozygous for the gene ank. This animal model bears a striking resemblance clinically, radiographically, and histologically to ankylosing spondylitis. Phosphocitrate (PC) is the only treatment known to significantly delay disease progression in MPA. Transforming growth factor-beta (TGF-beta) is important for both developmental bone formation and fracture healing, and has been detected in biopsy specimens from sacroiliac joints of patient with ankylosing spondylitis. We hypothesized that TGF-beta might be involved in the pathogenesis of MPA.

METHODS:

We compared the proliferative response of resting fibroblasts from normal and MPA mice to TGF-beta 1 as measured by 3H-thymidine incorporation and the effect of PC on that response. Cells were cultured with 10% serum as a positive control. The mouse fibroblast cell line, BALB/3T3, controlled for culture conditions.

RESULTS:

MPA and normal fibroblasts responded similarly to serum. MPA fibroblasts proliferated significantly better in TGF-beta 1 than the poorly responsive normal mouse fibroblasts. PC, at 10(-3) mol/L, inhibited the TGF-beta 1-induced proliferation of MPA and 3T3 cells, but had no effect on normal fibroblasts.

CONCLUSIONS:

MPA fibroblasts proliferate excessively to TGF beta 1 in vitro. This effect could be caused by altered TGF receptors, changes in signal transduction, or impaired inhibition of the TGF-beta signal. This excessive response is blocked by PC. These results give further clues as to how PC inhibits the progression of ankylosis in MPA.

• Authors: H E Krug
• Journal: Journal of investigative medicine : the official publication of the American Federation for Clinical Research (J Investig Med) Vol. 46 Issue 4 Pg. 134-9 (Apr 1998) ISSN: 1081-5589 [Print] England
• PMID: 9635372 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Citrates
• Transforming Growth Factor beta
• phosphocitrate

Topics

• 3T3 Cells
• Animals
• Ankylosis (pathology)
• Cell Division (drug effects)
• Citrates (pharmacology)
• Dose-Response Relationship, Drug
• Fibroblasts (drug effects)
• Mice
• Transforming Growth Factor beta (pharmacology)