Cytokine Profile From the Ligamentum Flavum in Patients with Ossification of the Posterior Longitudinal Ligament in the Cervical Spine

Abstract

Study design: Histological, immunohistochemical, and suspension array analyses of cytokine expression in human cervical ossification of the posterior longitudinal ligament (OPLL).

Objectives: The aim of this study was to determine whether changes in the cytokine profile reflect the maturation of chondrocytes and osteoblasts are associated with OPLL development.

Summary of background data: OPLL progresses gradually over a prolonged period and may lead to serious spinal cord complications. However, treatment methods only include conservative therapy for neurological symptoms or surgical decompression, whereas preventive therapy for OPLL remains nonexistent.

Methods: Ligamentous samples were harvested from 24 patients with OPLL who underwent spinal surgery, and five control samples from cervical spondylotic myelo/radiculopathy patients without OPLL. Tissue sections were used for immunohistochemical studies and primary cells were cultured from the ligamentous samples for cytokine profiling. Using a suspension array system, concentrations of 27 inflammatory cytokines or growth factors were measured to generate the cytokine profiles.

Results: Suspension array and immunoblot analysis revealed significant increments in the levels of interleukin (IL)-6, IL-1α, basic fibroblast growth factor, and RANTES in patients with OPLL. Immunohistochemical analysis further revealed that these factors were present in mesenchymal cells within the degenerative portion of the ligamentous matrix.

Conclusion: Our findings suggest that specific changes in the cytokine profile during ossification promote osteoblast differentiation, thereby providing new insights into OPLL pathogenesis. Moreover, this work supports the development of a new therapeutic method for preventing OPLL progression by regulating the cytokine profiles.Level of Evidence: 3.