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Differentiation of Human Marrow Stromal Precursor Cells: Bone Morphogenetic Protein‐2 Increases OSF2/CBFA1, Enhances Osteoblast Commitment, and Inhibits Late Adipocyte Maturation
Author(s) -
Gori Francesca,
Thomas Thierry,
Hicok Kevin C.,
Spelsberg Thomas C.,
Riggs B. Lawrence
Publication year - 1999
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.1999.14.9.1522
Subject(s) - osteoblast , endocrinology , bone morphogenetic protein 2 , medicine , adipocyte , stromal cell , osteocalcin , biology , cellular differentiation , bone marrow , microbiology and biotechnology , chemistry , alkaline phosphatase , adipose tissue , biochemistry , gene , in vitro , enzyme
Because regulation of the differentiation to osteoblasts and adipocytes from a common progenitor in bone marrow stroma is poorly understood, we assessed effects of bone morphogenetic protein‐2 (BMP‐2) on a conditionally immortalized human marrow stromal cell line, hMS(2–6), which is capable of differentiation to either lineage. BMP‐2 did not affect hMS(2–6) cell proliferation but enhanced osteoblast differentiation as assessed by a 1.8‐fold increase in expression of OSF2/CBFA1 (a gene involved in commitment to the osteoblast pathway), by increased mRNA expression and protein secretion for alkaline phosphatase (ALP), type I procollagen and osteocalcin (OC) (except for OC protein), and by increased mineralized nodule formation. Transient transfection with Osf2/Cbfa1 antisense oligonucleotide substantially reduced BMP‐2–stimulated expression of ALP mRNA and protein. The effects of BMP‐2 on adipocyte differentiation varied: expression of peroxisome proliferator‐activated receptor γ2 (a gene involved in commitment to the adipocyte pathway) was unchanged, mRNA expression of the early differentiation marker, lipoprotein lipase, was increased, and mRNA and protein levels of the late differentiation marker, leptin, and the formation of cytoplasmic lipid droplets were decreased. Thus, by enhancing osteoblast commitment and by inhibiting late adipocyte maturation, BMP‐2 acts to shunt uncommitted marrow stromal precursor cells from the adipocyte to the osteoblast differentiation pathway.