title: Insulin receptor isoforms are differently expressed during human osteoblastogenesis.
abstract: The reciprocal influence and bidirectional cross-talk between bone and energy metabolism is a recent finding, since the discovery that the product of osteoblasts osteocalcin increases pancreatic β-cell proliferation, insulin secretion and sensitivity. Conversely, the anabolic effect of insulin is crucial for osteoblast function, as suggested by severe osteopenia and increased incidence of fracture in insulin-deficient diabetic patients. The Insulin Receptor (IR) tyrosine kinase, which is commonly expressed in the insulin-sensitive liver, muscle, and adipose tissues, is also found in animal and human bone. Here we show that in human bone two insulin receptor isoforms (IR-A and IR-B) are differently expressed. Mature human osteoblasts predominantly express IR-B, whereas IR-A is mainly expressed in osteoblast precursors, and IR-B/IR-A mRNA ratio significantly increases along the osteogenic differentiation of mesenchymal stromal precursors. Moreover, transfected osteoprogenitors overexpressing IR-A show an increased proliferation rate. In contrast, when transfected with and overexpressing IR-B, their proliferation rate is reduced, corresponding to a more differentiated phenotype. In conclusion, the fine regulation of the expression of different isoforms of IR during osteogenic differentiation confirms the important role played by IR in bone homeostasis, providing the basis for new perspectives on the various involvements of IR isoforms in bone pathophysiology.
authors.affiliation: Laboratory for Orthopaedic Pathophysiology and Regenerative Medicine, Istituto Ortopedico Rizzoli, Bologna, Italy.
authors.forename: Sofia
authors.initials: S
authors.lastname: Avnet
authors.forename: Francesca
authors.initials: F
authors.lastname: Perut
authors.forename: Manuela
authors.initials: M
authors.lastname: Salerno
authors.forename: Laura
authors.initials: L
authors.lastname: Sciacca
authors.forename: Nicola
authors.initials: N
authors.lastname: Baldini
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D001842:Bone and Bones / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics*; D002460:Cell Line; D049109:Cell Proliferation; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism; D010012:Osteogenesis / Q000235:genetics*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014162:Transfection
chemical_list: D015703:Antigens, CD; D020033:Protein Isoforms; C435941:INSR protein, human; D011972:Receptor, Insulin; D000469:Alkaline Phosphatase