Resumo

LOPEZ-HERRADON, A. et al. Comparison of the osteogenic actions of parathyroid hormone-related protein (PTHrP) in diabetic and insulin-like growth factor-I (IGF-I) deficient mouse models. Rev Osteoporos Metab Miner [online]. 2014, vol.6, n.2, pp.46-56. ISSN 2173-2345.  https://dx.doi.org/10.4321/S1889-836X2014000200004.

Diabetes mellitus (DM) is a metabolic pathology characterised by chronic hyperglycemia due to a deficit in the production and/or action of insulin. DM, above all type I, is commonly associated with osteopenia/osteoporosis and with an increased risk of fractures. Insulin-like growth factor-I (IGF-I), a factor abundant in the bone matrix which plays a significant role in the development and maintenance of bone mass, diminishes with DM. Parathyroid hormone-related protein (PTHrP), a modulator of growth and osteoblast function, acts on osteoprogenitors, promoting osteoblast differentiation and bone regeneration. Its expression is reduced in the presence of DM. In this work we have evaluated and compared the osteogenic actions of PTHrP in mouse models with type 1 DM and IGF-I deficiency. Diabetic mice by injection of streptozotocin had a reduction in bone mass in the long bones associated with an increase in oxidised proteins and a reduction in the expression of genes related to the Wnt pathway and of β-catenin protein, as well as alterations in vertebral trabecular bone. In the mouse model with IGF-I deficit our results indicate the presence of osteopenia both in the femur (associated with an inhibition of the Wnt pathway) and the spine (L1-L5). Our findings demonstrate that the administration of PTHrP, predominantly through its N-terminal domain, modulates the canonical Wnt pathway in relation to its osteogenic actions in a diabetic situation and also, in part, in the absence of IGF-I.

Palavras-chave : PTHrP; diabetes mellitus; IGF-I; osteopenia; Wnt pathway.

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