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Critical Reviews™ in Eukaryotic Gene Expression
Facteur d'impact: 2.156 Facteur d'impact sur 5 ans: 2.255 SJR: 0.649 SNIP: 0.599 CiteScore™: 3

ISSN Imprimer: 1045-4403
ISSN En ligne: 2162-6502

Critical Reviews™ in Eukaryotic Gene Expression

DOI: 10.1615/CritRevEukaryotGeneExpr.v13.i24.90
10 pages

Serum Levels of TGF-b and Fibronectin in Autosomal Dominant Osteopetrosis in Relation to Underlying Mutations and Well-Described Murine Counterparts

Jens Bollerslev
Department of Endocrinology, National University Hospital, N-0027 Oslo, Norway; and School of Medicine and Pharmacology, University of Western Australia, Nedlands, 6009 WA, Australia
Thor Ueland
Department of Endocrinology and Research Institute for Internal Medicine, National University Hospital, N-0027 Oslo, Norway
Paul R. Odgren
Dept. of Cell Biology, University of Massachusetts Medical School, Worcester, MA 01655

RÉSUMÉ

The study gives a further biochemical description of two different forms of autosomal dominant osteopetrosis (ADO) in relation to murine counterparts, with special attention to osteoblast function and the recent discovery of LRP5 gene mutations in ADO I. Patients and controls were investigated for markers of bone formation and resorption at baseline and following stimulation with thyroid hormone. Moreover, four different well-described murine models of osteopetrosis were investigated.
Concerning the human forms, serum TSH levels decreased in all subjects, indicating effects on the target tissue. Osteocalcin and cross-linked collagen (NTx) were without significant differences among the groups. Significant increases in both markers were seen following stimulation. Baseline active TGF-b1 levels were increased in both types of ADO (60% in ADO I [P = 0.006]; 46% in ADO II [P = 0.001], respectively), whereas fibronectin levels were decreased in both (ADO I 58% and ADO II 63% of normal, respectively [P = 0.012 and P = 0.001]). Following treatment, levels increased temporarily in all groups. In the murine models, active TGF-b1 was significantly decreased in the tl- and ia-rat, whereas fibronectin levels were decreased in the mi-mouse, however, increased in the ia-rat.
In conclusion, both types of ADO showed the same qualitative biochemical differences compared to controls, except that OPG levels were higher in ADO I. The decreased fibronectin levels in both types and in murine models reflect decreased bone resorption; however, this may also indicate hitherto unrecognized alterations in bone formation. Biochemical differences among known syndromes related to mutations in the LRP5 gene indicate different underlying pathogenetic mechanisms.


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