Osteopontin

Osteopontin, also known as secreted phosphoprotein 1 (SPP1), is a multifunctional matricellular protein involved in bone remodeling, immune regulation, and inflammation. In humans, the SPP1 gene on chromosome 4 encodes osteopontin. The protein exists in several isoforms produced by alternative splicing, including OPN-a (the canonical form), OPN-b, and OPN-c, with tissue-specific expression patterns.

Osteopontin is a highly phosphorylated, acidic secreted protein rich in serine and threonine residues. It contains an Arg-Gly-Asp (RGD) integrin-binding motif and a thrombin cleavage site that generates N- and C-terminal fragments with distinct receptor interactions. It is produced by osteoblasts and osteoclasts in bone, as well as by macrophages, T cells, and other cell types under various physiological and pathophysiological conditions.

Functions include promoting adhesion and migration of cells, modulating survival, and facilitating mineralization by binding to hydroxyapatite in bone. Through interactions with integrins (such as αvβ3, αvβ5) and CD44, it influences cell adhesion, signaling, and cytokine production. Cleavage fragments and different isoforms can modulate receptor engagement and activity, contributing to context-specific effects.

In disease, osteopontin participates in inflammatory and fibrotic processes, cardiovascular disease, kidney disease, and cancer progression. Circulating and tissue levels of osteopontin are often elevated in inflammatory states and can correlate with disease activity or prognosis in certain cancers. It is used as a biomarker in research and, in some settings, clinically.

Genetic and animal studies show osteopontin contributes to bone resorption and remodeling; mice lacking OPN exhibit altered bone turnover and reduced osteoclast attachment to mineral. Therapeutic strategies targeting osteopontin pathways are under investigation.