Pregled bibliografske jedinice broj: 351767
Neurofibromatosis type 1 gene haploinsufficiency reduces AP-1 gene expression without abrogating the anabolic effect of parathyroid hormone.
Neurofibromatosis type 1 gene haploinsufficiency reduces AP-1 gene expression without abrogating the anabolic effect of parathyroid hormone. // "Calcif Tissue Int"[Journal], 78 (2006), 162-170 (podatak o recenziji nije dostupan, članak, ostalo)
CROSBI ID: 351767 Za ispravke kontaktirajte CROSBI podršku putem web obrasca
Naslov
Neurofibromatosis type 1 gene haploinsufficiency reduces AP-1 gene expression without abrogating the anabolic effect of parathyroid hormone.
Autori
Yu X ; Milas J ; Watanabe N ; Rao N ; Murthy S ; Potter OL ; Wenning MJ ; Clapp WD ; Hock JM.
Izvornik
"Calcif Tissue Int"[Journal] (0353-3735) 78
(2006);
162-170
Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, ostalo
Ključne riječi
parathyroid hormone; neurofibromatosis
Sažetak
Approximately 50% of neurofibromatosis type 1 (NF1) patients exhibit skeletal pathology, such as premature osteoporosis or pseudoarthroses. Loss of neurofibromin deregulates Ras signal transduction to affect generation of mitogen-activated protein kinase and Akt, both of which have been implicated in parathyroid hormone (PTH) anabolic mechanisms. Our aim was to determine if loss of neurofibromin impaired the anabolic effect of PTH on bone mass. Nf1 heterozygote (Nf1(+/-)) and wild type (Nf1(+/+)) mice were treated with recombinant human PTH(1-34) or vehicle once daily for 3-28 days. PTH enhanced mRNA expression of c-fos, junB, and fra2 in the distal femur metaphyses of both genotypes ; expression of these transcripts was consistently lower in PTH-treated Nf1(+/-) mice. Despite lowered c-fos expression in Nf1(+/-) mice, PTH increased bone mass equivalently in both genotypes by 28 days. Ex vivo, Nf1 heterozygosity was associated with increased inducible osteoclasts in PTH-treated bone marrow cells and impairment of the actin stress fiber and cyclic adenosine monophosphate response to PTH in osteoprogenitors. Lower c-fos expression was previously thought to abrogate PTH responsiveness. Our results suggest crosstalk might occur between Ras signal transduction and the protein kinase A pathway in Nf1(+/-) mice. Ras signal transduction does not appear to be essential for the anabolic actions of PTH on bone. Because PTH was effective in the absence of Nf1, it may offer a useful approach to treat osteoporosis in NF1 patients.
Izvorni jezik
Engleski
Znanstvena područja
Kliničke medicinske znanosti
POVEZANOST RADA
Ustanove:
Medicinski fakultet, Osijek
