Isolation and characterization of a novel plasma membrane protein, osteoblast induction factor (obif), associated with osteoblast differentiation

We identify a novel gene, obif (osteoblast induction factor), encoding a transmembrane protein that is predominantly expressed in osteoblasts. During mouse development, obif is initially observed in the limb bud in a complementary pattern to Sox9 expression. Later in development, obif is highly expressed in osteoblasts at the stage of endochondral ossification. In cell line models, obif is up-regulated during osteoblastic differentiation. Exogenous obif expression stimulates osteoblastic differentiation and obif knockdown inhibits osteoblastic differentiation in preosteblastic MC3T3-E1 cells. In addition, the extracellular domain of obif protein exhibits functions similar to the full-length obif protein in induction of MC3T3-E1 differentiation.Our results suggest that obif plays a role in osteoblastic differentiation by acting as a ligand.The skeleton is a multifunctional system with physiological roles in providing a rigid framework and support, acting as the primary storage site for mineral salts, and functioning in hematopoiesis. While several cell types are known to contribute to bone formation, the major player is a common bone matrix-secreting cell type, the osteoblast.Chondrocytes, which play critical roles at several stages of endochondral ossification, and osteoblasts are derived from common precursors, and both intrinsic cues and signals from extrinsic cues play critical roles in the lineage decision of these cell types [1-3]. The targeted mutation of Runx2 or Osterix, transcription regulators highly expressed in osteoblast progenitors, result in the lack of mature osteoblasts, demonstrating that these factors are essential for osteoblastogenesis [4-7]. Several studies have shown that cell fate commitment within the osteoblast lineage requires sequential, stage-specific, Ihh and canonical Wnt/β-catenin signaling to promote osteoblastic, and also to block chondrogenic, differentiation programs [8-11]. Another recent report shows that the inhibitory effect o