Circulating sclerostin and dickkopf-1 levels in ossification of the posterior longitudinal ligament of the spine

Kashii, Masafumi; Matuso, Yohei; Sugiura, Tetsuro; Fujimori, Takahito; Nagamoto, Yukitaka; Makino, Takahiro; Kaito, Takashi; Ebina, Kosuke; Iwasaki, Motoki; Yoshikawa, Hideki

doi:10.1007/s00774-015-0671-5

Cited by 25 publications

(35 citation statements)

References 37 publications

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“…3 ). Consistent with the model of Kashii et al [ 37 ], we suggest that the higher serum SOST levels are counterbalanced by underproduction of DKK1. Fifty percent of the patients with DISH also have OPLL, and OPLL is thought to be a subtype of DISH [ 38 ].…”

Section: Discussionsupporting

confidence: 91%

“…SOST plays a critical role in bone and mineral metabolism. Kashii et al [ 37 ] showed that systemic secretion of SOST increases with higher bone mass in men with OPLL and that serum SOST levels negatively correlate with DKK1 levels in men with OPLL. Higher serum SOST levels are counterbalanced by underproduction of DKK1 [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

“…Kashii et al [ 37 ] showed that systemic secretion of SOST increases with higher bone mass in men with OPLL and that serum SOST levels negatively correlate with DKK1 levels in men with OPLL. Higher serum SOST levels are counterbalanced by underproduction of DKK1 [ 37 ]. In the present study, we found that the DKK-1 levels were significantly lower in patients with OPLL than those in controls.…”

Section: Discussionmentioning

confidence: 99%

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Correlation of blood bone turnover biomarkers and Wnt signaling antagonists with AS, DISH, OPLL, and OYL

Niu

Lin

Yuan

et al. 2017

BMC Musculoskelet Disord

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BackgroundWnt signaling plays an important role in development and maintenance of many organs and tissues. The most-studied secreted Wnt inhibitors are sclerostin (SOST), Dickkopf-related protein 1 (DKK-1), and secreted frizzled related protein 1 (SFRP-1) which play important roles in bone turnover. The present study investigated the relationship between serum Wnt inhibitors and diseases with excessive ossification structures, such as ossification of posterior longitudinal ligament (OPLL), ankylosing spondylitis (AS), diffuse idiopathic skeletal hyperostosis (DISH), and ossification of yellow ligament (OYL).MethodsTwenty-five patients with AS, DISH, OPLL, or OYL were recruited in this study. Fasting peripheral blood samples were collected from all patients and nine controls. Various biomarkers of bone turnover including osteocalcin (OSC), osteoprotegerin (OPG), SFRP-1, DKK-1, and SOST were investigated.ResultsOur data showed that serum levels of OSC were higher, but Dkk-1 levels were lower in AS, DISH, OPLL, and OYL patients than those in the controls. Serum levels of SFRP-1 were significantly higher in DISH patients than those in the controls. Serum levels of SOST were significantly higher in DISH and OPLL patients than both levels in the controls. Serum levels of OPG were lower in AS patients than those in the controls. Serum levels of OSC were higher in the OPLL patients than those in the AS patients. Serum levels of DKK-1, SFRP-1, SOST, and OPG were not significantly different between the different disease groups.ConclusionsIn this exploratory study, both OSC and DKK-1 levels are correlated with the clinical conditions associated with excessive ossification, indicating that blood OSC and DKK-1 levels may serve as diagnostic biomarkers for AS, DISH, OPLL, and OYL. These findings may also help discover potential drug therapies for management of these diseases in the future.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Correlation of blood bone turnover biomarkers and Wnt signaling antagonists with AS, DISH, OPLL, and OYL

Niu

Lin

Yuan

et al. 2017

BMC Musculoskelet Disord

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“…Serum sclerostin and DKK1 levels are negatively correlated in male OPLL subjects. Systemic secretion of sclerostin also increases with advancing age and with higher bone mass in male OPLL subjects [ 84 ].…”

Section: Opll Biomarkersmentioning

confidence: 99%

The Pathogenesis of Ossification of the Posterior Longitudinal Ligament

Yan

Gao²,

Liu

et al. 2017

Aging and disease

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Ossification of the posterior longitudinal ligament (OPLL) is a multi-factorial disease involving an ectopic bone formation of spinal ligaments. It affects 0.8-3.0% aging Asian and 0.1-1.7% aging European Caucasian. The ossified ligament compresses nerve roots in the spinal cord and causes serious neurological problems such as myelopathy and radiculopathy. Research in understanding pathogenesis of OPLL over the past several decades have revealed many genetic and non-genetic factors contributing to the development and progress of OPLL. The characterizations of aberrant signaling of bone morphogenetic protein (BMP) and mitogen-activated protein kinases (MAPK), and the pathological phenotypes of OPLL-derived mesenchymal stem cells (MSCs) have provided new insights on the molecular mechanisms underlying OPLL. This paper reviews the recent progress in understanding the pathophysiology of OPLL and proposes future research directions on OPLL.

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“…At present, several genetic and non-genetic factors are involved in the pathological progress of OPLL. Aberrant levels of broblast growth factor-23 [3], leptin [4], dickkopf-1 and sclerostin [5], as well as mechanical stress signaling have been identi ed as main contributing factors in the development of OPLL [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Autophagy in spinal ligament fibroblasts: evidence and possible implications for ossification of the posterior longitudinal ligament

Yang

Lin

Chen

et al. 2020

Preprint

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Background: The molecular mechanisms of ossification of the posterior longitudinal ligament (OPLL) remains to be elucidated. The aim of the present study was to investigate the autophagy of spinal ligament fibroblasts derived from patients with OPLL and to examine whether autophagy associated gene expression was correlated with the expression of osteogenic differentiation genes. Methods: Expression of autophagy associated genes was detected in 37 samples from 21 OPLL patients and 16 non-OPLL patients. The correlation of autophagy associated gene expression and the expression of osteogenic differentiation genes was analyzed by Pearson’s correlation. The expression of autophagy associated genes of ligament fibroblasts was assessed by reverse transcription-quantitative Polymerase Chain Reaction (RT-qPCR), western blotting and immunofluorescence. The incidence of autophagy was assessed by flow cytometry. After knockdown using small interfering RNA targeting Beclin1, the expression of osteogenic differentiation genes were compared in spinal ligament fibroblasts. Results: In clinical specimens, mRNA expression levels of microtubule-associated protein 1 light chain 3 and Beclin1 were higher in the OPLL group compared with the non-OPLL group. Pearson correlation analysis demonstrated that Beclin1 expression was positively correlated with expression of osteocalcin (OCN) (r=0.8233, P<0.001), alkaline phosphatase, biomineralization associated (ALP) (r=0.7821, P<0.001) and collagen type 1 (COL 1) (r=0.6078, P=0.001). Consistently, the upregulation of autophagy associated genes in ligament fibroblasts from patients with OPLL were further confirmed by western blotting and immunofluorescence. The incidence of autophagy was also increased in ligament fibroblasts from patients with OPLL. Furthermore, knockdown of Beclin1 led to a decrease in the expression of OCN, ALP and COL 1 by 63.2% (P<0.01), 52% (P<0.01) and 53.2% (P<0.01) in ligament fibroblasts from patients with OPLL, respectively. Conclusions: Beclin1-mediated autophagy was involved in the osteogenic differentiation of ligament fibroblasts, and promoted the development of OPLL.

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Circulating sclerostin and dickkopf-1 levels in ossification of the posterior longitudinal ligament of the spine

Cited by 25 publications

References 37 publications

Correlation of blood bone turnover biomarkers and Wnt signaling antagonists with AS, DISH, OPLL, and OYL

Correlation of blood bone turnover biomarkers and Wnt signaling antagonists with AS, DISH, OPLL, and OYL

The Pathogenesis of Ossification of the Posterior Longitudinal Ligament

Autophagy in spinal ligament fibroblasts: evidence and possible implications for ossification of the posterior longitudinal ligament

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