Dataset Information

Clinical characteristics in patients with ossification of the posterior longitudinal ligament: A prospective multi-institutional cross-sectional study.

ABSTRACT: Ossification of the posterior longitudinal ligament (OPLL) can occur throughout the entire spine and can sometimes lead to spinal disorder. Although patients with OPLL sometimes develop physical limitations because of pain, the characteristics of pain and effects on activities of daily living (ADL) have not been precisely evaluated in OPLL patients. Therefore, we conducted a multi-center prospective study to assess whether the symptoms of cervical OPLL are different from those of cervical spondylosis (CS). A total of 263 patients with a diagnosis of cervical OPLL and 50 patients with a diagnosis of CS were enrolled and provided self-reported outcomes, including responses to the Japanese Orthopaedic Association (JOA) Cervical Myelopathy Evaluation Questionnaire (JOACMEQ), JOA Back Pain Evaluation Questionnaire (JOABPEQ), visual analog scale (VAS), and SF-36 scores. The severity of myelopathy was significantly correlated with each domain of the JOACMEQ and JOABPEQ. There was a negative correlation between the VAS score for each domain and the JOA score. There were significantly positive correlations between the JOA score and the Mental Health, Bodily Pain, Physical Functioning, Role Emotional, and Role Physical domains of the SF-36. One-to-one matching resulted in 50 pairs of patients with OPLL and CS. Although there was no significant between-group difference in scores in any of the domains of the JOACMEQ or JOABPEQ, the VAS scores for pain or numbness in the buttocks or limbs were significantly higher in the CS group; however, there was no marked difference in low back pain, chest tightness, or numbness below the chest between the two study groups. The scores for the Role Physical and Body Pain domains of the SF-36 were significantly higher in the OPLL group than in the CS group, and the mean scores for the other domains was similar between the two groups. The results of this study revealed that patients with OPLL were likely to have neck and low back pain and restriction in ADL. No specific type of pain was found in patients with OPLL when compared with those who had CS.

SUBMITTER: Hirai T

PROVIDER: S-EPMC7099083 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Clinical characteristics in patients with ossification of the posterior longitudinal ligament: A prospective multi-institutional cross-sectional study.

Hirai Takashi T Yoshii Toshitaka T Ushio Shuta S Mori Kanji K Maki Satoshi S Katsumi Keiichi K Nagoshi Narihito N Takeuchi Kazuhiro K Furuya Takeo T Watanabe Kei K Nishida Norihiro N Watanabe Kota K Kaito Takashi T Kato Satoshi S Nagashima Katsuya K Koda Masao M Ito Kenyu K Imagama Shiro S Matsuoka Yuji Y Wada Kanichiro K Kimura Atsushi A Ohba Tetsuro T Katoh Hiroyuki H Matsuyama Yukihiro Y Ozawa Hiroshi H Haro Hirotaka H Takeshita Katsushi K Watanabe Masahiko M Matsumoto Morio M Nakamura Masaya M Yamazaki Masashi M Okawa Atsushi A Kawaguchi Yoshiharu Y

Scientific reports 20200326 1

Ossification of the posterior longitudinal ligament (OPLL) can occur throughout the entire spine and can sometimes lead to spinal disorder. Although patients with OPLL sometimes develop physical limitations because of pain, the characteristics of pain and effects on activities of daily living (ADL) have not been precisely evaluated in OPLL patients. Therefore, we conducted a multi-center prospective study to assess whether the symptoms of cervical OPLL are different from those of cervical spondy ...[more]

PMID: 32218490

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Project description:Ossification of the posterior longitudinal ligament (OPLL), a spinal ligament, reduces the range of motion in limbs. No treatment is currently available for OPLL, which is why therapies are urgently needed. OPLL occurs in obesity, is more common in men, and has an onset after 40 years of age. The mechanisms underlying OPLL remain unclear. In this study, we performed a serum proteomic analysis in both OPLL patients and healthy subjects to identify factors potentially involved in the development of OPLL, and found reduced levels of a protein that might underlie the pathology of OPLL. We isolated the protein, determined its amino acid sequence, and identified it as chemokine (C-X-C motif) ligand 7 (CXCL7). Based on these proteomics findings, we generated a CXCL7 knockout mouse model to study the molecular mechanisms underlying OPLL. CXCL7-null mice presented with a phenotype of OPLL, showing motor impairment, heterotopic ossification in the posterior ligament tissue, and osteoporosis in vertebrate tissue. To identify the mechanisms of CXCL7 deficiency in OPLL, we searched for single nucleotide polymorphisms and altered DNA exons, but no abnormalities were found. Although miR-340 levels were found to be high in an miRNA array, they were insufficient to reduce CXCL7 levels. Ubiquitin C-terminal hydrolase1 (UCHL1) was found to be overexpressed in CXCL7-null mice and in the sera of patients with OPLL, and was correlated with OPLL severity. Post-translational modifications of proteins with ubiquitin and ubiquitin-like modifiers, orchestrated by a cascade of specialized ubiquitin activating enzyme (E1), ubiquitin conjugating enzyme (E2), and ubiquitin ligase (E3) enzymes, are thought to control a wide range of cellular processes, and alterations in the ubiquitin-proteasome system have been associated with several degenerative disorders. In addition, the OPLL tissue of CXCL7-null mouse and its primary cells expressed the antibody to ubiquitin (linkage-specific K48). Our data clearly show decreased CXCL7 levels in patients with OPLL, and that OPLL developed in mice lacking CXCL7. Tumor necrosis factor receptor-associated factor (TRAF)6 expression was decreased in CXCL7-null mouse primary cells. Furthermore, K48 polyubiquitination was found in posterior longitudinal ligament ossified tissue and primary cells from CXCL7-null mice. We performed a phosphoproteomics analysis in CXCL7-deficient mice and identified increased phosphorylation of mitogen-activated protein kinase kinase (ME3K)15, ubiquitin protein ligase E3C (UBE3C) and protein kinase C (PKC) alpha, suggesting that ubiquitin-dependent degradation is involved in CXCL7 deficiency. Future studies in the CXCL7-null mouse model are, therefore, warranted to investigate the role of ubiquitination in the onset of OPLL. In conclusion, CXCL7 levels may be useful as a serum marker for the progression of OPLL. This study also suggests that increasing CXCL7 levels in patients can serve as an effective therapeutic strategy for the treatment of OPLL.

Dataset Information

Clinical characteristics in patients with ossification of the posterior longitudinal ligament: A prospective multi-institutional cross-sectional study.

Publications

Clinical characteristics in patients with ossification of the posterior longitudinal ligament: A prospective multi-institutional cross-sectional study.

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