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Mechanical stress induces elastic fibre disruption and cartilage matrix increase in ligamentum flavum.

ABSTRACT: Lumbar spinal stenosis (LSS) is one of the most frequent causes of low back pain and gait disturbance in the elderly. Ligamentum flavum (LF) hypertrophy is the main pathomechanism of LSS, but the reason for its occurrence is not clearly elucidated. In this study, we established a novel animal model of intervertebral mechanical stress concentration and investigated the biological property of the LF. The LF with mechanical stress concentration showed degeneration with elastic fibres disruption and cartilage matrix increase, which are similar to the findings in hypertrophied LF from patients with LSS. By contrast, decreased Col2a1 expression was found in the LF at fixed levels, in which mechanical stress was strongly reduced. These findings indicate that mechanical stress plays a crucial role in LF hypertrophy through cartilage matrix increase. The findings also suggest that fusion surgery, which eliminates intervertebral instability, may change the property of the LF and lead to the relief of patients' symptoms.

SUBMITTER: Hayashi K

PROVIDER: S-EPMC5638934 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Mechanical stress induces elastic fibre disruption and cartilage matrix increase in ligamentum flavum.

Hayashi Kazunori K Suzuki Akinobu A Abdullah Ahmadi Sayed S Terai Hidetomi H Yamada Kentaro K Hoshino Masatoshi M Toyoda Hiromitsu H Takahashi Shinji S Tamai Koji K Ohyama Shoichiro S Javid Akgar A Suhrab Rahmani Mohammad M Hasib Maruf Mohammad MM Nakamura Hiroaki H

Scientific reports 20171012 1

Lumbar spinal stenosis (LSS) is one of the most frequent causes of low back pain and gait disturbance in the elderly. Ligamentum flavum (LF) hypertrophy is the main pathomechanism of LSS, but the reason for its occurrence is not clearly elucidated. In this study, we established a novel animal model of intervertebral mechanical stress concentration and investigated the biological property of the LF. The LF with mechanical stress concentration showed degeneration with elastic fibres disruption and ...[more]

PMID: 29026131

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Project description: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.

Dataset Information

Mechanical stress induces elastic fibre disruption and cartilage matrix increase in ligamentum flavum.

Publications

Mechanical stress induces elastic fibre disruption and cartilage matrix increase in ligamentum flavum.

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