Leptin acts on human marrow stromal cells to enhance differentiation to osteoblasts and to inhibit differentiation to adipocytes

Thierry Thomas, Francesca Gori, Sundeep Khosla, Michael Dennis Jensen, Bartolome Burguera, B. Lawrence Riggs

Research output: Contribution to journalArticle

596 Citations (Scopus)

Abstract

Both bone mass and serum leptin levels are increased in obesity. Because osteoblasts and adipocytes arise from a common precursor in bone marrow, we assessed the effects of human recombinant leptin on a conditionally immortalized human marrow stromal cell line, hMS212, with the potential to differentiate to either the osteoblast or adipocyte phenotypes. By RT-PCR and Western immunoblot analysis, the hMS2-12 cells expressed messenger RNA (mRNA) and protein for the leptin receptor. Leptin did not affect hMS2-12 cell proliferation, but resulted in dose- and time-dependent increases in mRNA and protein levels of alkaline phosphatase, type I collagen, and osteocalcin, and in a 59% increase in mineralized matrix. Leptin increased mRNA levels of lipoprotein lipase at 3 days, but decreased mRNA levels of adipsin and leptin at 9 days and decreased lipid droplet formation by 50%. Leptin did not affect the expression of Cbfa1 or peroxisome proliferator-activated receptor-γ2, transcription factors involved in commitment to the osteoblast and adipocyte pathways, respectively. Thus, leptin acts on human marrow stromal cells to enhance osteoblast differentiation and to inhibit adipocyte differentiation. Our data support the hypothesis that leptin is a previously unrecognized, physiological regulator of these two differentiation pathways, acting primarily on maturation of stromal cells into both lineages.

Original languageEnglish (US)
Pages (from-to)1630-1638
Number of pages9
JournalEndocrinology
Volume140
Issue number4
StatePublished - 1999

Fingerprint

Stromal Cells
Leptin
Osteoblasts
Adipocytes
Bone Marrow
Messenger RNA
Complement Factor D
Leptin Receptors
Peroxisome Proliferator-Activated Receptors
Lipoprotein Lipase
Osteocalcin
Collagen Type I
Alkaline Phosphatase
Proteins
Transcription Factors
Obesity
Western Blotting
Cell Proliferation
Phenotype
Bone and Bones

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Leptin acts on human marrow stromal cells to enhance differentiation to osteoblasts and to inhibit differentiation to adipocytes. / Thomas, Thierry; Gori, Francesca; Khosla, Sundeep; Jensen, Michael Dennis; Burguera, Bartolome; Riggs, B. Lawrence.

In: Endocrinology, Vol. 140, No. 4, 1999, p. 1630-1638.

Research output: Contribution to journalArticle

Thomas, Thierry ; Gori, Francesca ; Khosla, Sundeep ; Jensen, Michael Dennis ; Burguera, Bartolome ; Riggs, B. Lawrence. / Leptin acts on human marrow stromal cells to enhance differentiation to osteoblasts and to inhibit differentiation to adipocytes. In: Endocrinology. 1999 ; Vol. 140, No. 4. pp. 1630-1638.
@article{f7d98a34f61a4efe967bb971099e106c,
title = "Leptin acts on human marrow stromal cells to enhance differentiation to osteoblasts and to inhibit differentiation to adipocytes",
abstract = "Both bone mass and serum leptin levels are increased in obesity. Because osteoblasts and adipocytes arise from a common precursor in bone marrow, we assessed the effects of human recombinant leptin on a conditionally immortalized human marrow stromal cell line, hMS212, with the potential to differentiate to either the osteoblast or adipocyte phenotypes. By RT-PCR and Western immunoblot analysis, the hMS2-12 cells expressed messenger RNA (mRNA) and protein for the leptin receptor. Leptin did not affect hMS2-12 cell proliferation, but resulted in dose- and time-dependent increases in mRNA and protein levels of alkaline phosphatase, type I collagen, and osteocalcin, and in a 59{\%} increase in mineralized matrix. Leptin increased mRNA levels of lipoprotein lipase at 3 days, but decreased mRNA levels of adipsin and leptin at 9 days and decreased lipid droplet formation by 50{\%}. Leptin did not affect the expression of Cbfa1 or peroxisome proliferator-activated receptor-γ2, transcription factors involved in commitment to the osteoblast and adipocyte pathways, respectively. Thus, leptin acts on human marrow stromal cells to enhance osteoblast differentiation and to inhibit adipocyte differentiation. Our data support the hypothesis that leptin is a previously unrecognized, physiological regulator of these two differentiation pathways, acting primarily on maturation of stromal cells into both lineages.",
author = "Thierry Thomas and Francesca Gori and Sundeep Khosla and Jensen, {Michael Dennis} and Bartolome Burguera and Riggs, {B. Lawrence}",
year = "1999",
language = "English (US)",
volume = "140",
pages = "1630--1638",
journal = "Endocrinology",
issn = "0013-7227",
publisher = "The Endocrine Society",
number = "4",

}

TY - JOUR

T1 - Leptin acts on human marrow stromal cells to enhance differentiation to osteoblasts and to inhibit differentiation to adipocytes

AU - Thomas, Thierry

AU - Gori, Francesca

AU - Khosla, Sundeep

AU - Jensen, Michael Dennis

AU - Burguera, Bartolome

AU - Riggs, B. Lawrence

PY - 1999

Y1 - 1999

N2 - Both bone mass and serum leptin levels are increased in obesity. Because osteoblasts and adipocytes arise from a common precursor in bone marrow, we assessed the effects of human recombinant leptin on a conditionally immortalized human marrow stromal cell line, hMS212, with the potential to differentiate to either the osteoblast or adipocyte phenotypes. By RT-PCR and Western immunoblot analysis, the hMS2-12 cells expressed messenger RNA (mRNA) and protein for the leptin receptor. Leptin did not affect hMS2-12 cell proliferation, but resulted in dose- and time-dependent increases in mRNA and protein levels of alkaline phosphatase, type I collagen, and osteocalcin, and in a 59% increase in mineralized matrix. Leptin increased mRNA levels of lipoprotein lipase at 3 days, but decreased mRNA levels of adipsin and leptin at 9 days and decreased lipid droplet formation by 50%. Leptin did not affect the expression of Cbfa1 or peroxisome proliferator-activated receptor-γ2, transcription factors involved in commitment to the osteoblast and adipocyte pathways, respectively. Thus, leptin acts on human marrow stromal cells to enhance osteoblast differentiation and to inhibit adipocyte differentiation. Our data support the hypothesis that leptin is a previously unrecognized, physiological regulator of these two differentiation pathways, acting primarily on maturation of stromal cells into both lineages.

AB - Both bone mass and serum leptin levels are increased in obesity. Because osteoblasts and adipocytes arise from a common precursor in bone marrow, we assessed the effects of human recombinant leptin on a conditionally immortalized human marrow stromal cell line, hMS212, with the potential to differentiate to either the osteoblast or adipocyte phenotypes. By RT-PCR and Western immunoblot analysis, the hMS2-12 cells expressed messenger RNA (mRNA) and protein for the leptin receptor. Leptin did not affect hMS2-12 cell proliferation, but resulted in dose- and time-dependent increases in mRNA and protein levels of alkaline phosphatase, type I collagen, and osteocalcin, and in a 59% increase in mineralized matrix. Leptin increased mRNA levels of lipoprotein lipase at 3 days, but decreased mRNA levels of adipsin and leptin at 9 days and decreased lipid droplet formation by 50%. Leptin did not affect the expression of Cbfa1 or peroxisome proliferator-activated receptor-γ2, transcription factors involved in commitment to the osteoblast and adipocyte pathways, respectively. Thus, leptin acts on human marrow stromal cells to enhance osteoblast differentiation and to inhibit adipocyte differentiation. Our data support the hypothesis that leptin is a previously unrecognized, physiological regulator of these two differentiation pathways, acting primarily on maturation of stromal cells into both lineages.

UR - http://www.scopus.com/inward/record.url?scp=0032982438&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032982438&partnerID=8YFLogxK

M3 - Article

C2 - 10098497

AN - SCOPUS:0032982438

VL - 140

SP - 1630

EP - 1638

JO - Endocrinology

JF - Endocrinology

SN - 0013-7227

IS - 4

ER -