Fas-Ligand Expression on Nucleus Pulposus Begins in Developing Embryo

Inui, Yoshihiro; Nishida, Kotaro; Doita, Minoru; Takada, Toru; Miyata, Hiroshi; Yoshiya, Shinichi; Kurosaka, Masahiro

doi:10.1097/01.brs.0000143172.07771.fc

Cited by 23 publications

(17 citation statements)

References 20 publications

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“…29,30 Furthermore, the nucleus has been considered a relatively immune privileged site. 31 This is supported by our study in which the human bone marrow cells survived across a fully discordant barrier after xenogeneic transplantation for up to 42 days. The immune privileged characteristics are attributed to several factors.…”

supporting

confidence: 70%

The fate of transplanted xenogeneic bone marrow‐derived stem cells in rat intervertebral discs

Wei

Tao

Chung

et al. 2009

Journal Orthopaedic Research

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Intervertebral disc degeneration is a major cause and a risk factor for chronic low back pain. The potential of using stem cells to treat disc degeneration has been raised. The aims of our study were to assess whether xenogeneic bone-marrow derived stem cells could survive in a rat disc degeneration model and to determine which cell types, if any, survived and differentiated into disc-like cells. Human bone-marrow derived CD34 þ (hematopoietic progenitor cells) and CD34 À (nonhematopoietic progenitor cells, including mesenchymal stem cells) cells were isolated, fluorescent-labeled, and injected into rat coccygeal discs. The rats were sacrificed at day 1, 10, 21, and 42. Treated discs were examined by histological and immunostaining techniques and compared to control discs. The survival of transplanted cells was further confirmed with a human nuclear specific marker. Fluorescent labeled CD34 À cells were detected until day 42 in the nucleus pulposus of the injected discs. After 3 weeks these cells had differentiated into cells expressing chondrocytic phenotype . In contrast, the fluorescent labeled CD34 þ cells could not be detected after day 21. No fluorescence-positive cells were detected in the noninjected control discs. Further, no inflammatory cells infiltrated the nucleus pulposus, even though these animals had not received immunosuppressive treatment. Our data provide evidence that transplanted human BM CD34 À cells survived and differentiated within the relative immune privileged nucleus pulposus of intervertebral disc degeneration. ß

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supporting

confidence: 70%

The fate of transplanted xenogeneic bone marrow‐derived stem cells in rat intervertebral discs

Wei

Tao

Chung

et al. 2009

Journal Orthopaedic Research

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“…An in vitro study further confirmed the activation of caspase-8 in cultured rabbit annulus fibrosus (AF) cells [33]. Recently, it has been suggested that FasL plays different roles in normal and degenerative IVDs [34], which helps the formation of immune privilege in normal IVDs [35][36][37], and triggerring apoptosis in IVDD [34]. Rannou et al [38] demonstrated that the mechanical overload-induced IVDD was mediated through the mitochondrial apoptotic pathway in IVD cells from human samples and mouse models.…”

Section: Introductionmentioning

confidence: 70%

Role of death receptor, mitochondrial and endoplasmic reticulum pathways in different stages of degenerative human lumbar disc

et al. 2011

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Intervertebral disc (IVD) cell apoptosis has been suggested to play an important role in promoting the degeneration process. It has been demonstrated that IVD cell apoptosis occurs through either death receptor, mitochondrial or endoplasmic reticulum (ER) pathway. Our study aimed to explore the relationship among these three pathways and grade of IVD degeneration (IVDD). IVDs were collected from patients with lumbar fracture, vertebral tumor, disc herniation or spondylolisthesis. IVDs were distinguished by MRI and histomorphological examination, cell apoptosis was detected by TUNEL staining. Biomarkers of these three apoptosis pathways were detected by RT-PCR and Western blot. Furthermore, the correlation between apoptosis pathways biomarkers and disc pathology were analyzed. Nucleus pulposus cell density decreased with degeneration process, and increased apoptotic ratio. ER pathway was predominant in mild stage of IVDD (GRP78, GADD153 upregulation and caspase-4 activation), death receptor pathway was predominant in mild and moderate stages (Fas, FasL up-regulation and caspase-8 activation) and mitochondrial pathway was predominant in moderate and severe stages (Bcl-2 down-regulation, Bax up-regulation, cytochrome-c accumulation in cytoplasm and caspase-9 activation). There were significant differences in the expressions of Fas, FasL, Bax, GADD153, cytochrome-c and cleaved caspase-8/9/3 between contained and non-contained discs. In conclusion, apoptosis occurs via these three apoptosis pathways together in IVDD. ER pathway plays a more critical role in the mild compared to moderate and severe stages, death receptor pathway in mild and moderate, and mitochondrial pathway in moderate and severe stages of IVDD. Disc cells apoptosis may progress rapidly after herniation, and may depend on the type of herniation.

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“…We firstly evaluated the expression of fas and fasl in zebrafish whole embryos and larvae. The expression of fas and fasl in brain, eyes, gut and ovary of the adult fish is conserved in mammals, indicating a similar role for FAS/FASL during evolution [14, 40-43]. Interestingly, fasl expression is modulated during development while fas is expressed in all stages analyzed, suggesting the importance of a specific activation of this factor.…”

Section: Discussionmentioning

confidence: 99%

“…The apoptotic process is involved in normal notochord development in Xenopus laevis [11], and in particular the extrinsic apoptotic pathway is conserved and necessary for notochord development in zebrafish [12]. In addition, the expression of tumor necrosis factor receptor (TNFR) FAS and its ligand FASL , leads to the notochord cells regression in the adult rat intervertebral disks [13, 14]. The autocrine-paracrine interaction between Fas and Fasl results in the trimerization and activation of the Fas receptor, which leads the cell to apoptosis [15, 16].…”

Section: Introductionmentioning

confidence: 99%

FAS/FASL are dysregulated in chordoma and their loss-of-function impairs zebrafish notochord formation

et al. 2014

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Chordoma is a rare malignant tumor that recapitulates the notochord phenotype and is thought to derive from notochord remnants not correctly regressed during development. Apoptosis is necessary for the proper notochord development in vertebrates, and the apoptotic pathway mediated by Fas and Fasl has been demonstrated to be involved in notochord cells regression. This study was conducted to investigate the expression of FAS/FASL pathway in a cohort of skull base chordomas and to analyze the role of fas/fasl homologs in zebrafish notochord formation. FAS/FASL expression was found to be dysregulated in chordoma leading to inactivation of the downstream Caspases in the samples analyzed. Both fas and fasl were specifically expressed in zebrafish notochord sorted cells. fas and fasl loss-of-function mainly resulted in larvae with notochord multi-cell-layer jumps organization, larger vacuolated notochord cells, defects in the peri-notochordal sheath structure and in vertebral mineralization. Interestingly, we observed the persistent expression of ntla and col2a1a, the zebrafish homologs of the human T gene and COL2A1 respectively, which are specifically up-regulated in chordoma. These results demonstrate for the first time the dysregulation of FAS/FASL in chordoma and their role in notochord formation in the zebrafish model, suggesting their possible implication in chordoma onset.

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Fas-Ligand Expression on Nucleus Pulposus Begins in Developing Embryo

Cited by 23 publications

References 20 publications

The fate of transplanted xenogeneic bone marrow‐derived stem cells in rat intervertebral discs

The fate of transplanted xenogeneic bone marrow‐derived stem cells in rat intervertebral discs

Role of death receptor, mitochondrial and endoplasmic reticulum pathways in different stages of degenerative human lumbar disc

FAS/FASL are dysregulated in chordoma and their loss-of-function impairs zebrafish notochord formation

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