IGF-I receptor is required for the anabolic actions of parathyroid hormone on bone. 2007

Yongmei Wang, and Shigeki Nishida, and Benjamin M Boudignon, and Andrew Burghardt, and Hashem Z Elalieh, and Michelle M Hamilton, and Sharmila Majumdar, and Bernard P Halloran, and Thomas L Clemens, and Daniel D Bikle
Department of Medicine, Endocrine Unit, Veterans Affairs Medical Center, San Francisco, California 94121, USA.

We showed that the IGF-IR-null mutation in mature osteoblasts leads to less bone and decreased periosteal bone formation and impaired the stimulatory effects of PTH on osteoprogenitor cell proliferation and differentiation. BACKGROUND This study was carried out to examine the role of IGF-I signaling in mediating the actions of PTH on bone. METHODS Three-month-old mice with an osteoblast-specific IGF-I receptor null mutation (IGF-IR OBKO) and their normal littermates were treated with vehicle or PTH (80 microg/kg body weight/d for 2 wk). Structural measurements of the proximal and midshaft of the tibia were made by microCT. Trabecular and cortical bone formation was measured by bone histomorphometry. Bone marrow stromal cells (BMSCs) were obtained to assess the effects of PTH on osteoprogenitor number and differentiation. RESULTS The fat-free weight of bone normalized to body weight (FFW/BW), bone volume (BV/TV), and cortical thickness (C.Th) in both proximal tibia and shaft were all less in the IGF-IR OBKO mice compared with controls. PTH decreased FFW/BW of the proximal tibia more substantially in controls than in IGF-IR OBKO mice. The increase in C.Th after PTH in the proximal tibia was comparable in both control and IGF-IR OBKO mice. Although trabecular and periosteal bone formation was markedly lower in the IGF-IR OBKO mice than in the control mice, endosteal bone formation was comparable in control and IGF-IR OBKO mice. PTH stimulated endosteal bone formation only in the control animals. Compared with BMSCs from control mice, BMSCs from IGF-IR OBKO mice showed equal alkaline phosphatase (ALP)(+) colonies on day 14, but fewer mineralized nodules on day 28. Administration of PTH increased the number of ALP(+) colonies and mineralized nodules on days 14 and 28 in BMSCs from control mice, but not in BMSCs from IGF-IR OBKO mice. CONCLUSIONS Our results indicate that the IGF-IR null mutation in mature osteoblasts leads to less bone and decreased bone formation, in part because of the requirement for the IGF-IR in mature osteoblasts to enable PTH to stimulate osteoprogenitor cell proliferation and differentiation.

UI MeSH Term Description Entries
D009154 Mutation Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations. Mutations
D009929 Organ Size The measurement of an organ in volume, mass, or heaviness. Organ Volume,Organ Weight,Size, Organ,Weight, Organ
D010281 Parathyroid Hormone A polypeptide hormone (84 amino acid residues) secreted by the PARATHYROID GLANDS which performs the essential role of maintaining intracellular CALCIUM levels in the body. Parathyroid hormone increases intracellular calcium by promoting the release of CALCIUM from BONE, increases the intestinal absorption of calcium, increases the renal tubular reabsorption of calcium, and increases the renal excretion of phosphates. Natpara,PTH (1-84),PTH(1-34),Parathormone,Parathyrin,Parathyroid Hormone (1-34),Parathyroid Hormone (1-84),Parathyroid Hormone Peptide (1-34),Hormone, Parathyroid
D001835 Body Weight The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms. Body Weights,Weight, Body,Weights, Body
D001842 Bone and Bones A specialized CONNECTIVE TISSUE that is the main constituent of the SKELETON. The principal cellular component of bone is comprised of OSTEOBLASTS; OSTEOCYTES; and OSTEOCLASTS, while FIBRILLAR COLLAGENS and hydroxyapatite crystals form the BONE MATRIX. Bone Tissue,Bone and Bone,Bone,Bones,Bones and Bone,Bones and Bone Tissue,Bony Apophyses,Bony Apophysis,Condyle,Apophyses, Bony,Apophysis, Bony,Bone Tissues,Condyles,Tissue, Bone,Tissues, Bone
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001483 Base Sequence The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence. DNA Sequence,Nucleotide Sequence,RNA Sequence,DNA Sequences,Base Sequences,Nucleotide Sequences,RNA Sequences,Sequence, Base,Sequence, DNA,Sequence, Nucleotide,Sequence, RNA,Sequences, Base,Sequences, DNA,Sequences, Nucleotide,Sequences, RNA
D012333 RNA, Messenger RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal

Related Publications

Yongmei Wang, and Shigeki Nishida, and Benjamin M Boudignon, and Andrew Burghardt, and Hashem Z Elalieh, and Michelle M Hamilton, and Sharmila Majumdar, and Bernard P Halloran, and Thomas L Clemens, and Daniel D Bikle
September 2002, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research,
Yongmei Wang, and Shigeki Nishida, and Benjamin M Boudignon, and Andrew Burghardt, and Hashem Z Elalieh, and Michelle M Hamilton, and Sharmila Majumdar, and Bernard P Halloran, and Thomas L Clemens, and Daniel D Bikle
December 1993, Endocrine reviews,
Yongmei Wang, and Shigeki Nishida, and Benjamin M Boudignon, and Andrew Burghardt, and Hashem Z Elalieh, and Michelle M Hamilton, and Sharmila Majumdar, and Bernard P Halloran, and Thomas L Clemens, and Daniel D Bikle
March 2008, The Journal of biological chemistry,
Yongmei Wang, and Shigeki Nishida, and Benjamin M Boudignon, and Andrew Burghardt, and Hashem Z Elalieh, and Michelle M Hamilton, and Sharmila Majumdar, and Bernard P Halloran, and Thomas L Clemens, and Daniel D Bikle
June 2005, Endocrinology,
Yongmei Wang, and Shigeki Nishida, and Benjamin M Boudignon, and Andrew Burghardt, and Hashem Z Elalieh, and Michelle M Hamilton, and Sharmila Majumdar, and Bernard P Halloran, and Thomas L Clemens, and Daniel D Bikle
June 2015, Current opinion in pharmacology,
Yongmei Wang, and Shigeki Nishida, and Benjamin M Boudignon, and Andrew Burghardt, and Hashem Z Elalieh, and Michelle M Hamilton, and Sharmila Majumdar, and Bernard P Halloran, and Thomas L Clemens, and Daniel D Bikle
October 2002, Endocrinology,
Yongmei Wang, and Shigeki Nishida, and Benjamin M Boudignon, and Andrew Burghardt, and Hashem Z Elalieh, and Michelle M Hamilton, and Sharmila Majumdar, and Bernard P Halloran, and Thomas L Clemens, and Daniel D Bikle
November 2011, Journal of endocrinological investigation,
Yongmei Wang, and Shigeki Nishida, and Benjamin M Boudignon, and Andrew Burghardt, and Hashem Z Elalieh, and Michelle M Hamilton, and Sharmila Majumdar, and Bernard P Halloran, and Thomas L Clemens, and Daniel D Bikle
August 1997, Trends in endocrinology and metabolism: TEM,
Yongmei Wang, and Shigeki Nishida, and Benjamin M Boudignon, and Andrew Burghardt, and Hashem Z Elalieh, and Michelle M Hamilton, and Sharmila Majumdar, and Bernard P Halloran, and Thomas L Clemens, and Daniel D Bikle
November 2016, Bone,
Yongmei Wang, and Shigeki Nishida, and Benjamin M Boudignon, and Andrew Burghardt, and Hashem Z Elalieh, and Michelle M Hamilton, and Sharmila Majumdar, and Bernard P Halloran, and Thomas L Clemens, and Daniel D Bikle
February 2013, Clinical calcium,
Copied contents to your clipboard!