Osteonectin
(ON, OSN)

Secreted protein, acidic and rich in cysteine (SPARC)
BM-40

Gene: ON maps to 5q31-q33 and is polymorphic (Swaroop A. et al., 1988; Naylor S.L. et al., 1989).
mRNA: two polyadenylated transcripts of 2.2 and 3.0 kb were detected in human tissues and cultured cells by Northern blot analysis. The 2133-bp sequence of the more abundant (major) transcript contains an open reading frame for 303 amino acids. The larger and minor 3.0-kb mRNA has an identical coding region but utilizes a downstream polyadenylation signal (Swaroop A. et al., 1988).
Protein: a phosphorylated, acidic, glycine-rich, Ca²⁺-binding domains-containing glycoprotein. The function of this protein, conserved in evolution, remains partly unknown, but it may be involved in cell proliferation, repair of tissue damage, and morphogenetic processes such as modeling of extracellular matrix.
In bone, ON binds selectively to hydroxyapatite and to collagen fibrils at distinct sites. The protein accounts for the unique property of bone collagen to undergo calcification (Termine J.D. et al., 1981).
ON can be expressed by the endothelium in response to certain types of injury, induces rounding in adherent endothelial cells in vitro. From the results of studies on its influence on endothelial permeability, ON appears to regulate endothelial barrier function through F-actin-dependent changes in cell shape, coincident with the appearance of intercellular gaps, that provide a paracellular pathway for extravasation of macromolecules (Goldblum S.E. et al., 1994).
Platelets also contain and secrete ON (Stenner D.D. et al., 1986).

Cell lines:
- OSN was found to induce MMP2 activation in two invasive breast cancer cell (BCC) lines (MDA-MB-231 and BT-549) but not in a noninvasive counterpart (MCF-7), which lacks MMP14 (MT1-MMP) -an important determinant of MMP2 activation. The activity of OSN was restricted to a peptide corresponding to the NH₂-terminal region of the protein (Gilles C. et al., 1998).

Tumors:
- OSN mRNA and protein expression were determined in breast tumour biopsies and compared with estrogen receptor (ER) and progesterone receptor (PgR) levels in the same tumours. An inverse correlation was seen between OSN mRNA expression and ER level. Samples with low ER protein expression had a mean OSN mRNA level which was almost 4-fold greater than the mean level of expression observed in tumours containing high concentrations of ER protein. This inverse correlation was statistically significant. Despite the strong inverse relationship between OSN mRNA levels and tumour ER content, no correlation was seen when OSN protein concentration was measured in tumour cytosols on immunoblots and compared to ER and PgR levels in the same tumours. However, since it is a secreted protein, OSN protein expression may not reflect cellular OSN levels in breast tumours (Graham J.D. et al., 1997).

Findlay D.M. et al. (1988) Isolation of the osteonectin gene: evidence that a variable region of the osteonectin molecule is encoded within one exon. Biochemistry 27, 1483-1489.
Gilles C. et al. (1998) SPARC/osteonectin induces matrix metalloproteinase 2 activation in human breast cancer cell lines. Cancer Res. 58, 5529-5536.
Goldblum S.E. et al. (1994) SPARC (secreted protein acidic and rich in cysteine) regulates endothelial cell shape and barrier function. Proc. Natl. Acad. Sci. USA 91, 3448-3452.
Graham J.D. et al. (1997) Expression of osteonectin mRNA in human breast tumours is inversely correlated with oestrogen receptor content. Eur. J. Cancer 33, 1654-1660.
Naylor S.L. et al. (1989) The human osteonectin gene on chromosome 5 is polymorphic. (abstract) Cytogenet. Cell Genet. 51, 1051.
Stenner D.D. et al. (1986) Human platelets contain and secrete osteonectin, a major protein of mineralized bone. Proc. Natl. Acad. Sci. USA 83, 6892-6896.
Swaroop A. and Francke U. (1987) Molecular cloning, cDNA sequence, and expression of human SPARC (osteonectin). (abstract) Am. J. Hum. Genet. 41, A240.
Swaroop A. et al. (1988) Molecular analysis of the cDNA for human SPARC/osteonectin/BM-40: sequence, expression, and localization of the gene to chromosome 5q31-q33. Genomics 2, 37-47.
Termine J.D. et al. (1981) Osteonectin, a bone-specific protein linking mineral to collagen. Cell 26, 99-105.