IL-1beta, TNF-alpha, TGF-beta, and bFGF expression in bone biopsies before and after parathyroidectomy.
BACKGROUND
There is growing evidence pointing to an involvement of cytokines and growth factors in renal osteodystrophy. In this study, the expression of interleukin-l beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta), and basic fibroblast growth factor (bFGF) in bone biopsies taken from uremic patients before and 1 year after parathyroidectomy (PTX) was evaluated. Biochemical features and histomorphometric outcome were also studied.


METHODS
Iliac bone biopsies were taken before and 1 year after PTX in nine uremic patients with severe hyperparathyroidism (HPT). Immunohistochemical techniques were used to identify the expression of IL-1 beta, TNF-alpha, TGF-beta, and bFGF in these bone samples.


RESULTS
At the time of the second bone biopsy, the mean serum total alkaline phosphatase activity was normal, whereas mean serum intact parathyroid hormone (iPTH) level was slightly above the upper limit of normal values. Histomorphometric analysis showed a decrease in resorption parameters and static bone formation parameters after PTX. Dynamically, mineral apposition rate (MAR) and mineralization surface (MS/BS) decreased significantly. There was a marked local expression of IL-1beta, TNF-alpha, TGF-beta, and bFGF in bone biopsies before PTX, particularly in fibrous tissue and resorption areas. One year after PTX, IL-1beta decreased from 23.6 +/- 7.5% to 9.9 +/- 3.1%, TNF-alpha from 4.5 +/- 1.5% to 0.7 +/- 0.8%, TGF-beta from 49.6 +/- 9.8% to 15.2 +/- 4.6%, and bFGF from 50.9 +/- 12.7% to 12.9 +/- 7.9% (P < 0.001). A significant correlation was documented between cytokines and growth factors expression in bone with iPTH levels before and after PTX (P < 0.05).


CONCLUSIONS
Based on these results, we suggest that IL-1beta, TNF-alpha, TGF-beta, and bFGF are involved in bone remodeling regulation, acting as local effectors, possibly under the control of PTH.
Santos
Francisco R Lello
FR
Nephrology Division, University of São Paulo, São Paulo, Brazil.
Moysés
Rosa M A
RM
Montenegro
Fábio L M
FL
Jorgetti
Vanda
V
Noronha
Irene L
IL
D000293:Adolescent; D000328:Adult; D001706:Biopsy; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology; D012080:Chronic Kidney Disease-Mineral and Bone Disorder / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D016105:Parathyroidectomy; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D014511:Uremia / Q000378:metabolism / Q000473:pathology
D007375:Interleukin-1; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016222:Fibroblast Growth Factor 2