Elevated Serum Levels of IGF-1 Are Sufficient to Establish Normal Body Size and Skeletal Properties Even in the Absence of Tissue IGF-1

Autor: Yingjie Wu, Robert J. Majeska, Hui Sun, Clifford J. Rosen, Hayden William Courtland, Sebastien Elis, Karl J. Jepsen, Shoshana Yakar
Přispěvatelé: Division of Endocrinology, Diabetes and Bone Disease, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Maine Medical Center Research Institute (MMCRI), Leni and Peter W May Department of Orthopaedics, City College of New York [CUNY] (CCNY), City University of New York [New York] (CUNY)
Jazyk: angličtina
Rok vydání: 2010
Předmět:
Genetically modified mouse
medicine.medical_specialty
Ratón
Endocrinology
Diabetes and Metabolism

Transgene
medicine.medical_treatment
[SDV]Life Sciences [q-bio]
Osteoclasts
030209 endocrinology & metabolism
Cell Count
Biology
Body size
transgenic mice
mechanical properties
bone
Models
Biological

Bone and Bones
law.invention
03 medical and health sciences
Mice
0302 clinical medicine
Insulin resistance
law
Internal medicine
Periosteum
Gene expression
Paracrine Communication
medicine
IGF-1KO
Animals
Body Size
Orthopedics and Sports Medicine
Sexual Maturation
micro-computed tomography
Insulin-Like Growth Factor I
030304 developmental biology
0303 health sciences
Osteoblasts
Growth factor
medicine.disease
Biomechanical Phenomena
endocrine IGF-1
Autocrine Communication
Endocrinology
Animals
Newborn

Gene Expression Regulation
Recombinant DNA
IGF-1
Original Article
Zdroj: Journal of Bone and Mineral Research
Journal of Bone and Mineral Research, American Society for Bone and Mineral Research, In press, 26 (5), pp.1257-1266. ⟨10.1002/jbmr.20⟩
ISSN: 1523-4681
0884-0431
DOI: 10.1002/jbmr.20⟩
Popis: Use of recombinant insulin-like growth factor 1 (IGF-1) as a treatment for primary IGF-1 deficiency in children has become increasingly common. When untreated, primary IGF-1 deficiency may lead to a range of metabolic disorders, including lipid abnormalities, insulin resistance, and decreased bone density. To date, results of this therapy are considered encouraging; however, our understanding of the role played by IGF-1 during development remains limited. Studies on long-term treatment with recombinant IGF-1 in both children and animals are few. Here, we used two novel transgenic mouse strains to test the long-term effects of elevated circulating IGF-1 on body size and skeletal development. Overexpression of the rat igf1 transgene in livers of mice with otherwise normal IGF-1 expression (HIT mice) resulted in approximately threefold increases in serum IGF-1 levels throughout growth, as well as greater body mass and enhanced skeletal size, architecture, and mechanical properties. When the igf1 transgene was overexpressed in livers of igf1 null mice (KO-HIT), the comparably elevated serum IGF-1 failed to overcome growth and skeletal deficiencies during neonatal and early postnatal growth. However, between 4 and 16 weeks of age, increased serum IGF-1 fully compensated for the absence of locally produced IGF-1 because body weights and lengths of KO-HIT mice became comparable with controls. Furthermore, micro-computed tomography (µCT) analysis revealed that early deficits in skeletal structure of KO-HIT mice were restored to control levels by adulthood. Our data indicate that in the absence of tissue igf1 gene expression, maintaining long-term elevations in serum IGF-1 is sufficient to establish normal body size, body composition, and both skeletal architecture and mechanical function. © 2010 American Society for Bone and Mineral Research.
Databáze: OpenAIRE