Osteopontin as a Biomarker or Experimental Target for Outcomes After Ischemic Stroke: A Systematic Review of Human and Animal Studies
Lifeng Wu, Yanyan FuIntroduction:
Osteopontin (OPN), also known as secreted phosphoprotein-1 and encoded by the SPP1 gene, may be involved in inflammation, vascular injury, and tissue remodeling after ischemic stroke. This review synthesized and evaluated evidence on the associations between OPN or SPP1 and post-stroke outcomes in human and animal studies.
Method:
The literature search covered MEDLINE ALL, Embase, Web of Science Core Collection, the Cochrane Central Register of Controlled Trials, and Google Scholar, with each database searched from inception through 23 February 2026. Citation tracking was conducted up to 17 March 2026. Study selection, data extraction, and risk-of-bias assessment were performed independently by two reviewers, using QUIPS for human studies and SYRCLE’s tool for animal studies. Meta-analysis was planned when studies were sufficiently comparable; otherwise, findings were synthesized narratively. Certainty of evidence was assessed using GRADE where applicable. This systematic review was retrospectively registered with the Open Science Framework (OSF) Registries.
Results:
Eight studies reported in ten reports were included. Four human studies examined OPN measured within the first week after ischemic stroke in relation to functional outcome at 3 months. Higher OPN levels were consistently associated with poorer functional outcomes, but quantitative pooling was not performed because of substantial differences in OPN measurement and exposure modelling. Other human and animal studies supported a possible role of OPN in post-stroke prognosis and ischemic brain injury.
Discussion:
The evidence was limited by risk of bias and substantial differences in OPN measurement timing, sample type, cut-off values, exposure modelling, and outcomes.
Conclusion:
OPN may be associated with poorer outcomes after ischemic stroke, but its clinical utility remains uncertain. Larger prospective studies are needed.