Alterations of the Wnt/beta-catenin pathway and its target genes for the N- and C-terminal domains of parathyroid hormone-related protein in bone from diabetic mice.
Type 1 diabetes mellitus (T1D) is associated with bone loss. Given that the Wnt/beta-catenin pathway is a major regulator of bone accrual, we assessed this pathway in mice with streptozotozin-induced T1D. In diabetic mouse long bones, we found alterations favouring the suppression of this pathway by using PCR arrays and beta-catenin immunostaining. Downregulation of sclerostin, an inhibitor of this pathway, also occurred, and related to increased osteocyte apoptosis. Our data show that both N- and C-terminal parathyroid hormone-related peptide fragments might exert osteogenic effects in this setting by targeting several genes of this pathway and increasing beta-catenin in osteoblastic cells.
Portal-Núñez
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Laboratorio de Metabolismo Mineral y Oseo, Fundación Jiménez Díaz (Capio Group), Madrid, Spain.
Lozano
D
D
de Castro
L Fernández
LF
de Gortázar
A R
AR
Nogués
X
X
Esbrit
P
P
D000818:Animals; D017209:Apoptosis; D001851:Bone Diseases, Metabolic / Q000378:metabolism; D001842:Bone and Bones / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000378:metabolism; D015536:Down-Regulation; D017886:Durapatite / Q000378:metabolism / Q000494:pharmacology; D005796:Genes; D008297:Male; D051379:Mice; D010006:Osteoblasts / Q000378:metabolism; D010011:Osteocytes / Q000378:metabolism; D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein / Q000378:metabolism / Q000494:pharmacology; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology; D051176:beta Catenin / Q000378:metabolism* / Q000494:pharmacology
D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; D051176:beta Catenin; C023443:carboxyl-terminal parathyroid hormone; D017886:Durapatite