The Origin of Chondrocytes in the Nucleus Pulposus and Histologic Findings Associated With the Transition of a Notochordal Nucleus Pulposus to a Fibrocartilaginous Nucleus Pulposus in Intact Rabbit Intervertebral Discs

Kim, Ki-Won; Lim, Tae-Hong; Kim, Jesse G.; Jeong, Soon‐Taek; Masuda, Koichi; An, Howard S.

doi:10.1097/01.brs.0000061986.03886.4f

Cited by 160 publications

(127 citation statements)

References 28 publications

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“…Aggrecan consists of a core protein to which chondroitin sulfate and keratan sulfate (KS) are covalently linked. KS is reportedly a potential biomarker of IVD loading [16]. The regeneration ability of IVD tissue is limited.…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal Stem Cell and Nucleus Pulposus Cell Coculture Modulates Cell Profile

Niu

Yuan

Lin

et al. 2008

Clin Orthop Relat Res

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Spontaneous cell fusion can occur in cocultured stem cells. We examined whether telomerase activity change and cell fusion occurred in mesenchymal stem cell (MSC) and nucleus pulposus cell (NPC) coculture. MSCs and NPCs were labeled with PKH26 and PKH67 dyes and cocultured at a 50:50 ratio. An equal number of MSCs or NPCs were used as the control. After 14 days, cells were evaluated by cell growth, telomerase activity, quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), immunohistochemistry, and histologic observation. Cell fusion was confirmed by microscopic observation and fluorescence-activated cell sorter (FACS) analysis. The results suggested cell growth rate and telomerase activity were higher in cocultured cells than in NPCs cultured alone. The mRNA expression levels of the Type II collagen and aggrecan were elevated in cocultured cells. Immunohistochemical analysis revealed positive staining for Type II collagen and keratan sulfate in NPCs cultured alone and in a proportion of cocultured cells. Histologic observation revealed binucleated cocultured cells expressed both PKH dyes in the same location and slide focus. The FACS analysis revealed 42% of cocultured cells were doublestained. Cocultured cells partially maintained the NPC phenotype. The partially maintained phenotype of the NPCs may be attributable to spontaneous cell fusion in association with increased telomerase activity.

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Section: Introductionmentioning

confidence: 99%

Mesenchymal Stem Cell and Nucleus Pulposus Cell Coculture Modulates Cell Profile

Niu

Yuan

Lin

et al. 2008

Clin Orthop Relat Res

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“…The anulus fibrosus (AF) of the IVD is populated by fibrochondrocyte-like cells of mesenchymal origin, while the central-most nucleus pulposus (NP) is populated by both small chondrocyte-like cells of mesenchymal origin and larger, highly vacuolated cells derived from the notochord [22]. Notochordal cells in the nucleus pulposus begin to disappear shortly after birth and are replaced by fibrochondrocytic cells of the adjacent anulus fibrosus and cartilage endplate with age [6,14,20,23]. When isolated from most immature animal tissues, NP cells are presumed to contain many cells of notochordal origin [1,10,11,15,18] although some animal tissues retain notochordal cells well into maturity (e.g., rabbit, nonchondrodystrophoid dogs) [1].…”

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confidence: 99%

Molecular phenotypes of notochordal cells purified from immature nucleus pulposus

2006

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The immature nucleus pulposus (NP) is populated by cells of notochordal-origin that are larger and contain an extensive cytoskeletal network and numerous vacuoles. The disappearance of these cells with age is believed important in regulating metabolic shifts that may contribute to age-related disc degeneration. The precise biological function of these notochordal cells in the immature NP remains unclear, however, because of challenges in studying the mixed cell population in the NP. In this study, notochordallike cells were purified from immature NP cells using a new fluorescence-activated cell sorting (FACS) protocol with auto-fluorescence and size analysis. The unique molecular phenotypes of sorted notochordallike cells were characterized by the mRNA expression pattern for key matrix proteins and modulators, and by the expression of cell-matrix receptor integrin subunits. An FACS analysis showed that the immature NP contained a majority of cells that were larger than anulus fibrosus (AF) cells and with fluorescence higher than AF cells. In comparison with the small NP cells separated by the FACS protocol, sorted notochordal-like cells expressed lower mRNA levels of type I collagen, biglycan, TIMP1, HSP70 and c-fos, and did not express detectable mRNA levels of decorin, lumican, multiple MMPs or IL-1b via realtime quantitative RT-PCR. A greater number of these notochordal-like cells also expressed the higher levels of a6, a1 and b1 integrin subunits as compared to small NP cells. Together, our results point towards a unique molecular phenotype for these notochordal-like cells of NP, characterized by the absence of gene expression for specific small proteoglycans and higher protein expression of integrin subunits that regulate interactions with collagens and laminin. Future studies will be important for revealing if this unique molecular profile is coordinated with functional differences in pericellular matrix regions and/or integrin-mediated cell-matrix interactions for these notochordallike cells within the NP.

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“…This transition accompanies changes in cell types from notochordal cells to so-called chondrocyte-like cells. In humans, this transition is usually completed by the second decade [9]. In contrast to the chondrocytic phenotype of young notochordal cells, young AF cells are fibroblastic, which is phenotypically different, and they don't undergo chronological changes with age.…”

Section: Introductionmentioning

confidence: 99%

Accelerated premature stress-induced senescence of young annulus fibrosus cells of rats by high glucose-induced oxidative stress

Park

et al. 2014

International Orthopaedics (SICOT)

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Purposes Diabetes mellitus (DM) is thought to be an important aetiological factor in intervertebral disc degeneration. A glucose-mediated increase of oxidative stress is a major causative factor in development of diseases associated with DM. The aim of this study was to investigate the effect of high glucose on mitochondrial damage, oxidative stress and senescence of young annulus fibrosus (AF) cells. Methods AF cells were isolated from four-week-old young rats, cultured, and placed in either 10 % FBS (normal control) or 10 % FBS plus two different high glucose concentrations (0.1 M and 0.2 M) (experimental conditions) for one and three days. We identified and quantified the mitochondrial damage and reactive oxygen species (ROS) (oxidative stress). We also identified and quantified the occurrence of senescence and telomerase activity. Finally, the expressions of proteins were determined related to replicative senescence (p53-p21-pRB) and stress-induced senescence (p16-pRB). Results Two high glucoses enhanced the mitochondrial damage in young rat AF cells, which resulted in an excessive generation of ROS in a dose-and time-dependent manner for one and three days compared to normal control. Two high glucose concentrations increased the occurrence of senescence of young AF cells in a dose-and time-dependent manner. Telomerase activity declined in a dose-and timedependent manner. Both high glucose treatments increased the expressions of p16 and pRB proteins in young rat AF cells for one and three days. However, compared to normal control, the expressions of p53 and p21 proteins were decreased in young rat AF cells treated with both high glucoses for one and three days. Conclusions The present study demonstrated that high glucose-induced oxidative stress accelerates premature stress-induced senescence in young rat AF cells in a doseand time-dependent manner rather than replicative senescence. These results suggest that prevention of excessive generation of oxidative stress by strict blood glucose control could be important to prevent or to delay premature intervertebral disc degeneration in young patients with DM.

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The Origin of Chondrocytes in the Nucleus Pulposus and Histologic Findings Associated With the Transition of a Notochordal Nucleus Pulposus to a Fibrocartilaginous Nucleus Pulposus in Intact Rabbit Intervertebral Discs

Abstract: Chondrocytes in the intact rabbit nucleus pulposus originated and migrated from the cartilage endplate. The chondrocytes changed notochordal nucleus pulposus into fibrocartilaginous nucleus pulposus by depositing fibrocartilage lamellas and fibers in a centripetal direction.

Cited by 160 publications

References 28 publications

Mesenchymal Stem Cell and Nucleus Pulposus Cell Coculture Modulates Cell Profile

Mesenchymal Stem Cell and Nucleus Pulposus Cell Coculture Modulates Cell Profile

Molecular phenotypes of notochordal cells purified from immature nucleus pulposus

Accelerated premature stress-induced senescence of young annulus fibrosus cells of rats by high glucose-induced oxidative stress

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