Differentiation of human marrow stromal precursor cells: Bone morphogenetic protein-2 increases OSF2/CBFA1, enhances osteoblast commitment, and inhibits late adipocyte maturation

Because regulation of the differentiation to osteoblasts and adipocytes fro m a common progenitor in bone marrow stroma is poorly understood, we assess ed effects of bone morphogenetic protein-2 (BMP-2) on a conditionally immor talized human marrow stromal cell line, hMS(2-6), which is capable of diffe rentiation to either lineage. BMP-2 did not affect hMS(2-6) cell proliferat ion but enhanced osteoblast differentiation as assessed by a 1.8-fold incre ase in expression of OSF2/CBFA1 (a gene involved in commitment to the osteo blast pathway), by increased mRNA expression and protein secretion for alka line phosphatase (ALP), type I procollagen and osteocalcin (OC) (except for OC protein), and by increased mineralized nodule formation. Transient tran sfection with Osf2/Cbfa1 antisense oligonucleotide substantially reduced BM P-2-stimulated expression of ALP mRNA and protein,The effects of BMP-2 on a dipocyte differentiation varied: expression of peroxisome proliferator-acti vated receptor gamma 2 (a gene involved in commitment to the adipocyte path way) was unchanged, mRNA expression of the early differentiation marker, li poprotein lipase, was increased, and mRNA and protein levels of the late di fferentiation marker, leptin, and the formation of cytoplasmic lipid drople ts were decreased. Thus, by enhancing osteoblast commitment and by inhibiti ng late adipocyte maturation, BMP-2 acts to shunt uncommitted marrow stroma l precursor cells from the adipocyte to the osteoblast differentiation path way.