Possible Roles of CTGF/Hcs24 in the Initiation and Development of Ossification of the Posterior Longitudinal Ligament

Yamamoto, Yuji; Furukawa, Ken; Ueyama, Kazumasa; Nakanishi, Tohru; Takigawa, Masaharu; Harata, Seiko

doi:10.1097/00007632-200209010-00009

Cited by 49 publications

(31 citation statements)

References 14 publications

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“…Fibroblasts cells can differentiate into osteoblasts or osteocytes [4,8,9,12,24,28]. This differentiation should be accompanied by an upregulation of several marker genes related to bone formation, such as OCN, ALP and COL I.…”

Section: Discussionmentioning

confidence: 99%

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Upregulated expression of PERK in spinal ligament fibroblasts from the patients with ossification of the posterior longitudinal ligament

et al. 2013

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Purpose Molecular mechanism of ossification of the posterior longitudinal ligament (OPLL) remains unclear. This study was to investigate different expressions of PERK between the spinal ligament fibroblasts from OPLL patients and non-OPLL patients, and demonstrate knockdown of PERK protein expression by RNA interference inhibiting expression of osteocalcin (OCN), alkaline phosphatase (ALP), and type I collagen (COL I) in the cells from OPLL patients. Methods Spinal ligament cells were cultured using tissue fragment cell culture and identified by immunocytochemistry and immunofluorescence. The mRNA expression of osteoblast-specific genes of OCN, ALP and COL I was detected in the cells from OPLL and non-OPLL patients by semiquantitative reverse transcription-polymerase chain reaction. The protein expression of PERK was detected by Western blotting. And then, after 72 h, when RNA interference against PERK was performed on the cells from OPLL patients, expression of the osteoblast-specific genes was compared again between the transfection group and non-transfection group. Results Spinal ligament fibroblasts were observed 7-10 days after cell culture. Immunocytochemistry and immunofluorescence exhibited positive results of vimentin staining. The mRNA expressions of OCN, ALP and COL I and protein expression of PERK in the cells from OPLL patients were significantly greater than those from non-OPLL patients. In addition, knockdown of PERK protein expression inhibited the mRNA expressions of OCN, ALP and COL I remarkably in the transfection group compared with the non-transfection group, at 72 h after RNA interference targeting PERK was performed on the cells from OPLL patients. Conclusions The cultured fibroblasts from OPLL patients exhibited osteogenic characteristics, and PERKmediated ER stress might be involved in development of OPLL.

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Section: Discussionmentioning

confidence: 99%

“…These two processes might differ in terms of the speed of bone formation [6,31]. Although several studies have investigated the osteogenetic characteristic of the spinal ligament fibroblasts from OPLL patients, the intracellular signaling pathways still remain unclear [4,8,9,12,24,28].…”

Section: Introductionmentioning

confidence: 99%

Upregulated expression of PERK in spinal ligament fibroblasts from the patients with ossification of the posterior longitudinal ligament

et al. 2013

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“…It is unclear why thoracic myelopathy more often develops in middleaged people compared to cervical myelopathy patients. OLF and OPLL, the major causes of thoracic myelopathy, might be associated with some genetic factors (Koga et al 1998;Yamamoto et al 2002). The thoracic spine is naturally kyphotic and the spinal cord runs anterior of the spinal canal, which suggests the cord is more easily damaged from the anterior side.…”

Section: Discussionmentioning

confidence: 99%

Thoracic Myelopathy in Japan: Epidemiological Retrospective Study in Miyagi Prefecture during 15 Years

Aizawa

Sato²,

Tanaka

et al. 2006

Tohoku J. Exp. Med.

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E., NISHIHIRA T. and KOKUBUN, S. Thoracic Myelopathy in Japan: Epidemiological Retrospective Study in Miyagi Prefecture during 15Years. Tohoku J. Exp. Med., 210 (3),[199][200][201][202][203][204][205][206][207][208] Thoracic myelopathy is defined as spinal cord compression in the thoracic region, leading to sensory and motor dysfunctions in the trunk and lower extremities, and can be caused by various degenerative processes of the spine. Thoracic myelopathy is rare, and there are many unsolved problems including its epidemiological and clinical features. We have established a registration system of spinal surgeries, which covered almost all surgeries in Miyagi Prefecture, and enrolled the data of 265 patients with thoracic myelopathy from 1988 to 2002. The annual rate of surgery gradually increased and averaged 0.9 per 100,000 inhabitants, which was less than 1/10 of that for cervical myelopathy. About 20 patients with thoracic myelopathy are operated on in Miyagi Prefecture each year. It frequently develops in middle-aged males. About half of the cases were caused by ossification of the ligamentum flavum, followed by ossification of the posterior longitudinal ligament, intervertebral disc herniation and posterior spur. Patients usually noticed numbness or pain in the legs and the preoperative duration was long, averaging 2 years. Its symptomatic similarities to lumbar disorders might cause difficulty in making a correct diagnosis. Since thoracic myelopathy can markedly restrict the activities of daily life, even general physicians should recognize this entity. thoracic myelopathy; epidemiological study; ossification of the ligamentum flavum; ossification of the posterior longitudinal ligament

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“…Recent molecular genetic studies have identified several candidate genes that are differentially expressed in OPLL cells compared to normal ligament cells (15,16): reports suggest an increase in collagen, type VI, alpha 1 (Col6a1) (17,18); collagen type XI alpha 2 (Col11a2) (19,20); nucleotide pyrophosphatase (NPPS) (21 -24); leptin receptor (22); transforming growth factor-beta 1 (TGF-β1) (25 -27); promyelotic leukemia zinc finger (PLZF) (28,29); Tumor necrosis factor-alpha-stimulated gene 6 (TSG-6) (29); connective tissue growth factor (CTGF) (12); prostaglandin I 2 (PGI 2 ) (13) and endothelin-1 (30), amongst others. However, thus far, genetic factors have not been statistically linked to DISH or OPLL, most likely owing to the complexity of these diseases.…”

Section: Introductionmentioning

confidence: 99%

A Functional RNAi Screen for Runx2-Regulated Genes Associated With Ectopic Bone Formation in Human Spinal Ligaments

et al. 2008

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Abstract. Ossification of the posterior longitudinal ligament of the spine (OPLL) is characterized by ectopic ossification in the spinal ligaments, which enlarges with time and compresses the spinal cord, resulting in serious neurological symptoms. We previously reported that Runx2 expression was enhanced in spinal ligament cells from OPLL patients (OPLL cells). To clarify genes regulated by Runx2, Runx2 expression was first enhanced by culturing primary OPLL cells in osteogenic medium (OS induction) and then inhibited by siRNAs targeted to Runx2. DNA microarray demonstrated that in addition to chondrogenic factors such as connective tissue growth factor and cartilage oligomeric matrix protein, angiopoietin-1 was also significantly increased by OS induction and decreased by siRNAs for Runx2 in OPLL cells, suggesting that these genes are regulated by Runx2. However, these changes were not observed in non-OPLL control cells (from cervical spondylotic myelopathy patients). Furthermore, Runx2 was not decreased by siRNAs for angiopoietin-1. OS induction and RNAi inhibition of angiopoietin-1 expression was also observed in osteoblasts. Both siRNAs for Runx2 and angiopoietin-1 completely inhibited aggrecan-1 expression. These results suggest that angiopoietin-1 is downstream of Runx2 in both OPLL primary cells and osteoblasts. Angiopoietin-1 may play an important role in ectopic ossification.

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Possible Roles of CTGF/Hcs24 in the Initiation and Development of Ossification of the Posterior Longitudinal Ligament

Abstract: According to the study results, CTGF/Hcs24 may not only be an important factor in the development of endochondral ossification in OPLL, but may also be responsible for initiating osteogenesis in spinal ligament cells.

Cited by 49 publications

References 14 publications

Upregulated expression of PERK in spinal ligament fibroblasts from the patients with ossification of the posterior longitudinal ligament

Upregulated expression of PERK in spinal ligament fibroblasts from the patients with ossification of the posterior longitudinal ligament

Thoracic Myelopathy in Japan: Epidemiological Retrospective Study in Miyagi Prefecture during 15 Years

A Functional RNAi Screen for Runx2-Regulated Genes Associated With Ectopic Bone Formation in Human Spinal Ligaments

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