Altered bone microarchitecture in a type 1 diabetes mouse model Ins2 (Akita)

• Autor(a) principal: Pires De Carvalho, Filipe Ricardo
• Data de Publicação: 2018
• Outros Autores: Calado, Sofia, Silva, Gabriela A., Diogo, Gabriela S., Moreira da Silva, Joana, Reis, Rui L., Cancela, M. Leonor, Gavaia, Paulo
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10400.1/14540
• topic: Animals; Apoptosis; Biomarkers; Blood glucose; Body weight; Cancellous bone; Cartilage; Cortical bone; Diabetes mellitus; Disease models; Femur; Gene expression regulation; Growth plate; Insulin; Leptin; Male; Mice; Organ size; Tartrate-resistant acid phosphatase; Type 1; Inbred C57BL; Animal

Type 1 diabetes mellitus (T1DM) has been associated to several cartilage and bone alterations including growth retardation, increased fracture risk, and bone loss. To determine the effect of long term diabetes on bone we used adult and aging Ins2 Akita mice that developed T1DM around 3-4 weeks after birth. Both Ins2 Akita and wild-type (WT) mice were analyzed at 4, 6, and 12 months to assess bone parameters such as femur length, growth plate thickness and number of mature and preapoptotic chondrocytes. In addition, bone microarchitecture of the cortical and trabecular regions was measured by microcomputed tomography and gene expression of Adamst-5, Col2, Igf1, Runx2, Acp5, and Oc was quantified by quantitative real-time polymerase chain reaction. Ins2 Akita mice showed a decreased longitudinal growth of the femur that was related to decreased growth plate thickness, lower number of chondrocytes and to a higher number of preapoptotic cells. These changes were associated with higher expression of Adamst-5, suggesting higher cartilage degradation, and with low expression levels of Igf1 and Col2 that reflect the decreased growth ability of diabetic mice. Ins2 Akita bone morphology was characterized by low cortical bone area (Ct.Ar) but higher trabecular bone volume (BV/TV) and expression analysis showed a downregulation of bone markers Acp5, Oc, and Runx2. Serum levels of insulin and leptin were found to be reduced at all-time points Ins2 Akita . We suggest that Ins2 Akita mice bone phenotype is caused by lower bone formation and even lower bone resorption due to insulin deficiency and to a possible relation with low leptin signaling.