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Inflammatory Cytokines Induce Fibrosis and Ossification of Human Ligamentum Flavum Cells

 Jin-Oh Park  ;  Byung Ho Lee  ;  Young-Mi Kang  ;  Tae-Hwan Kim  ;  Ji Young Yoon  ;  Hyang Kim  ;  Un-Hye Kwon  ;  Kwang-Il Lee  ;  Hwan-Mo Lee  ;  Seong-Hwan Moon 
 Journal of Spinal Disorders & Techniques, Vol.26(1) : 6-12, 2013 
Journal Title
 Journal of Spinal Disorders & Techniques 
Issue Date
STUDY DESIGN: In vitro experiment using degenerated human ligamentum flavum (LF) and various inflammatory cytokines. OBJECTIVES: To examine the effect of inflammatory cytokines on LF cells and to identify their roles in the pathogenesis of LF hypertrophy and ossification. SUMMARY OF BACKGROUND DATA: Spinal stenosis is caused, in part, by hypertrophy and ossification of the LF, which are induced by the degenerative processes (ie, increased collagen synthesis and chondroid metaplasia) of ligament fibroblasts. Degenerated intervertebral disk spontaneously produces inflammatory cytokines, which might affect the adjacent LF through local milieu of the spinal canal. METHODS: The interlaminar portion of the LF was collected during surgical spinal procedures in 15 patients (age range, 49-78 y) with lumbar spinal stenosis. LF fibroblasts were isolated by enzymatic digestion of LF tissue. LF cell cultures were treated with various inflammatory cytokines: interleukin (IL)-1α, IL-6, tumor necrosis factor-α (TNF-α), prostaglandin E2 (PGE2), and nitric oxide (NO). Cytotoxicity was analyzed by MTT assays. DNA synthesis was measured with H-thymidine incorporation, and mRNA expression of types I, III, V, and XI collagen and osteocalcin were performed by reverse transcription-polymerase chain reaction. Histochemical stains such as Von Kossa were also performed to detect bone nodule formation. RESULTS: There was no cytotoxicity in the LF cells treated with each cytokine. There were significant increases in DNA synthesis and upregulated mRNA expression of types I, V, XI collagen and osteocalcin in LF cultures treated with various cytokines. LF cultures treated with IL-6, TNF-α, PGE2, and NO showed positive Von Kossa staining, indicating bone nodule formation from LF cells. CONCLUSIONS: Inflammatory cytokines (IL-6, TNF-α, PGE2, and NO) seem to play a crucial role in hypertrophy and ossification of LF. Degenerated, herniated intervertebral disks, and facet arthrosis may influence LF through inflammatory cytokines and cause hypertrophy and ossification of LF.
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1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Orthopedic Surgery (정형외과학교실)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원)
Yonsei Authors
강영미(Kang, Young Mi) ORCID logo https://orcid.org/0000-0002-7686-6316
김태환(Kim, Tae Hwan)
문성환(Moon, Seong Hwan)
박진오(Park, Jin Oh)
이병호(Lee, Byung Ho)
이환모(Lee, Hwan Mo) ORCID logo https://orcid.org/0000-0002-5405-3832
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