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

Background: 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 plays 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. Several studies have shown that cell fate commitment within the osteoblast lineage requires sequential, stage-specific signaling to promote osteoblastic differentiation programs. In osteoblastic differentiation, the functional mechanisms of transcriptional regulators have been well elucidated, however the exact roles of extrinsic molecules in osteoblastic differentiation are less clear.

Results: 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.

Conclusions: Our results suggest that obif plays a role in osteoblastic differentiation by acting as a ligand.