Abstract
Osteopontin is a member of the proinflammatory cytokine network, a complex system that involves many chemokines, cytokines, and growth factors. The aim of the present study was to study the associations between osteopontin and a large number of chemokines, cytokines, and growth factors. We analyzed plasma and urine osteopontin in 652 men from the Uppsala Longitudinal Study of Adult Men (ULSAM) study cohort and compared the levels with the levels of eighty-five chemokines, cytokines, and growth factors. We found significant associations between plasma osteopontin and 37 plasma biomarkers in a model adjusted for age, and 28 of those plasma biomarkers were significant in a model also adjusting for cardiovascular risk factors. There were no significant associations after Bonferroni adjustment between urine osteopontin and any of the studied plasma cytokine biomarkers. This study shows that circulating osteopontin participates in a protein–protein interaction network of chemokines, cytokines, and growth factors. The network contains responses, pathways, and receptor binding interactions relating to cytokines, regulation of the immune system, and also regulation of apoptosis and intracellular signal transduction.
Highlights
Osteopontin (OPN) was first identified in 1985 [1]
We investigated the associations between proinflammatory cytokines reported to be associated with cardiovascular diseases and osteopontin in plasma and urine to increase our knowledge on the interactions between osteopontin and soluble chemokines, cytokines, and growth factors
We found associations between plasma osteopontin and several inflammatory chemokines, cytokines, and growth factors
Summary
The name, osteopontin, indicates that the protein is expressed in bone, but it is secreted into plasma and urine and found in several other tissues. Osteopontin functions beyond those related to bone formation. Osteopontin has been implicated in several physiological and pathological processes such as bone turnover [2], cell survival [3], immune regulation and response [4], inflammation [5], ischemia [6], tissue remodeling [7], tumor progression [8], and wound healing [9]. Osteopontin acts as a proinflammatory cytokine, modulating the immune response by enhancing expression of Th1 cytokines [10]. Proinflammatory cytokines function within a complex network, stimulating the release of one another, including both cytokine agonists and antagonists. There is limited information on the interactions between osteopontin and other inflammatory chemokines, cytokines, and growth factors
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