Strong relationship between dyslipidemia and the ectopic ossification of the spinal ligaments

Endo, Tsutomu; Takahata, Masahiko; Fujita, Ryo; Koike, Yoshinao; Suzuki, Ryota; Hasegawa, Yoshinori; Murakami, Toshifumi; Ishii, Misaki; Yamada, Kei; Sudo, Hideki; Iwasaki, Norimasa

doi:10.1038/s41598-022-27136-4

Cited by 6 publications

(4 citation statements)

References 32 publications

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“…In addition, the study also found that many related serum markers may be related to the development of OPLL, Such as Sclerostin, Dickkopf-1 (DKK-1), Secreted Frizzled-Related Protein-1 (SFRP-1), etc [12]. Obesity and dyslipidemia has also been found to be closely related to the occurrence of OPLL [13,14]. However, there are still some limitations in the current research reports.…”

Section: Introductionmentioning

confidence: 85%

Inflammation in Ossification of the Posterior Longitudinal Ligament of Cervical spine:Monocytes increased significantly

Wu,

Wang,

et al. 2023

Preprint

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Objective: To investigate the expression of inflammatory cells in patients with Ossification of the Posterior Longitudinal Ligament of the Cervical spine (COPLL), and to explore the relationship between inflammation and COPLL. Methods: The study included 215 patients with OPLL and 184 control patients without COPLL. For the case-control analysis, 147 patients with COPLL and 147 demographically matched control patients without COPLL were included through PSM. The Leukocyte count, neutrophils, lymphocytes, monocytes, eosinophils, basophils, hs-CRP, EMR, and NLR were assessed. Furthermore, the relationship between the inflammatory cells and the extent of COPLL was analyzed.The data were also compared between the patients with different types of COPLL. Results: The peripheral blood mononuclear cells in the COPLL group were significantly higher than those in the control group. The hs-CRP in the continuous types ofCOPLL group was significantly higher than that in other subtypes. No correlation was found between any of the biomarkers and the extent of ossification. Conclusion: Compared with patients with simple cervical spondylosis, mononuclear cells in the peripheral blood of patients with cervical posterior longitudinal ligament ossification are significantly higher, suggesting that patients with cervical posterior longitudinal ligament ossification may be accompanied by a special inflammatory response.

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Section: Introductionmentioning

confidence: 85%

Inflammation in Ossification of the Posterior Longitudinal Ligament of Cervical spine:Monocytes increased significantly

Wu,

Wang,

et al. 2023

Preprint

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“…Hyperlipidemia has been studied as a potential driver of spinal ligament ossification. [ 16 18 19 ] The proportion of dyslipidemia in OPLL patients has been reported to be 1.6–2.2 times higher compared to controls. [ 18 ] Similarly, Fukada et al .…”

Section: Discussionmentioning

confidence: 99%

“…[ 16 18 19 ] The proportion of dyslipidemia in OPLL patients has been reported to be 1.6–2.2 times higher compared to controls. [ 18 ] Similarly, Fukada et al . reported a comorbidity of dyslipidemia in their OPLL group more than twice that of their control group (71.7% vs. 35.4%, respectively), with 64.1% of patients with diffuse OPLL having comorbid dyslipidemia.…”

Section: Discussionmentioning

confidence: 99%

Multilevel ossification of the posterior longitudinal ligament causing cervical myelopathy: An observational series of North American patients

Ledesma,

Issa,

Lambrechts

et al. 2023

Journal of Craniovertebral Junction and Spine

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Background: Few studies regarding ossification of the posterior longitudinal ligament (OPLL) outside of Asia currently exist in the literature. A set of patients with multilevel cervical OPLL causing symptomatic myelopathy or radiculopathy from a North American sample is analyzed. Objective: The objective of this study was to describe the demographics, radiographic findings, and surgical outcomes of a cohort of North American patients with degenerative spondylosis presenting for operative management of multilevel (>3 segments) cervical OPLL. Materials and Methods: Forty-three patients diagnosed with multilevel cervical OPLL and degenerative spondylosis presenting with symptomatic cervical myelopathy or radiculopathy were surgically treated over a 9-year period at a single tertiary care academic medical center. Radiographic measurements were performed on preoperative computed tomography and magnetic resonance imaging images of the cervical spine. Clinical outcomes included pre- and postoperative Nurick scores, 90-day readmission, complication, and revision surgery rates. Results: The mean age was 66.1 ± 10.9 years with a mean latest follow-up time of 32.7 ± 16.4 months. Most patients had previous diagnoses of obesity (70.7%) and hypertension (55.8%). At least one-quarter of patients were diagnosed with type 2 diabetes (34.9%), hyperlipidemia (41.9%), cardiovascular disease (25.6%), or chronic kidney disease (25.3%). The most common OPLL subtype was segmental (39.5%) and spanned a mean of 3.54 ± 1.48 segments. Myelopathic symptoms were present in 88.4% of patients. All patients experienced significant neurologic improvement at 3-week and latest follow-up ( P < 0.001 for both). Conclusions: Obesity, diabetes, and other metabolic derangements in patients with existing cervical spondylosis may be risk factors for a particularly aggressive form of multilevel OPLL. Various operative approaches may be employed to achieve adequate neurologic recovery. Further workup for OPLL in patients with these risk factors may prove beneficial to ensure appropriate operative management.

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“…The pathological process of TOLF involves fibrous tissue in the ligamentum flavum (LF) of the thoracic spine changing into osseous tissue, as characterized by typical endochondral ossification. 9 Previous studies found that stress stimuli, 10 , 11 degeneration, 12 genetics, 13 , 14 and endocrine metabolism 15 , 16 may be pathogenic factors of TOLF. However, the mechanism of occurrence and development of TOLF currently remain unclear.…”

Section: Introductionmentioning

confidence: 99%

M1 macrophage‐derived oncostatin M induces osteogenic differentiation of ligamentum flavum cells through the JAK2/STAT3 pathway

Yang,

Chen,

Fan

et al. 2023

JOR Spine

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BackgroundM1 macrophages (Mφs) are involved in osteogenic differentiation of ligamentum flavum (LF) cells and play an important role in heterotopic ossification. However, the mechanism by which M1 Mφs influence osteogenic differentiation of LF cells has not been studied.MethodsThe effect of conditioned medium including secretions of M1 Mφs (CM‐M1) on LF cells was analyzed by GeneChip profiling and ingenuity pathway analysis (IPA). THP‐1 cells were polarized into M1 Mφs and CM‐M1 was used to induce LF cells. In addition, LF cells were induced by CM‐M1 in the presence of cyclooxygenase 2 (COX‐2) inhibitors or oncostatin M (OSM)‐neutralizing antibodies. Based on the presence of OSM, knockout of OSMR or GP130 receptors, or addition of the Janus kinase 2 (JAK2) inhibitor AZD1480 or signal transducer and activator of transcription 3 (STAT3) inhibitor Stattic were examined for effects on osteogenic differentiation of LF cells. OSM secretion was quantified by ELISA, while qPCR and western blot were used to evaluate expression of osteogenic genes and receptor and signaling pathway‐related proteins, respectively.ResultsGeneChip and IPA results indicate that the OSM signaling pathway and its downstream signaling molecules JAK2 and STAT3 are significantly activated. ELISA results indicate that OSM is highly expressed in cells treated with CM‐M1 and lowly expressed in cells treated with CM‐M1 and a COX‐2 inhibitor. Besides, CM‐M1 induces osteogenic differentiation of LF cells, which is weakened when COX‐2 inhibitors or OSM‐neutralizing antibody are added to it. Recombinant OSM could induce osteogenic differentiation of LF cells and upregulate expression of OSMR, GP130, phosphorylated (P)‐JAK2, and P‐STAT3. Upon knockdown of OSMR or GP130, or the addition of AZD1480 or Stattic, P‐JAK2 and P‐STAT3 expression were decreased and osteogenic differentiation was reduced.ConclusionM1 Mφ‐derived OSM induces osteogenic differentiation of LF cells and the JAK2/STAT3 signaling pathway plays an important role.

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Strong relationship between dyslipidemia and the ectopic ossification of the spinal ligaments

Cited by 6 publications

References 32 publications

Inflammation in Ossification of the Posterior Longitudinal Ligament of Cervical spine:Monocytes increased significantly

Inflammation in Ossification of the Posterior Longitudinal Ligament of Cervical spine:Monocytes increased significantly

Multilevel ossification of the posterior longitudinal ligament causing cervical myelopathy: An observational series of North American patients

M1 macrophage‐derived oncostatin M induces osteogenic differentiation of ligamentum flavum cells through the JAK2/STAT3 pathway

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