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Biomedical subjects

Edward N Hanley

Publications and source records attributed to Edward N Hanley.

At least 19 recordsLinked to original sources
PubMed2006

Immunolocalization of thrombospondin in the human and sand rat intervertebral disc.

STUDY DESIGN: Human intervertebral disc tissue from the anulus was obtained in a prospective study investigating the presence of the matricellular protein thrombospondin (TSP) in human and sand rat discs. Studies were approved by the authors' Human Subjects Institutional Review Board and Institutional Animal Care and Use Committee. OBJECTIVES: To determine whether TSP could be detected in the human or sand rat disc with immunohistochemistry, and to assess its localization. SUMMARY OF BACKGROUND DATA: The role of the matricellular proteins in maintenance of disc health and extracellular matrix remodeling is as yet poorly understood. SPARC and tenascin have previously been shown to be present in the human disc. TSP has a well-recognized antiangiogenic activity in vivo and in vitro. METHODS: Sixteen specimens of human disc tissue and discs from 7 sand rats were assessed for immunohistochemical localization of TSP. Three human disc cell cultures grown in three-dimensional culture were also evaluated. RESULTS.: Strong immunoreactivity was present in the outer anulus of both human and sand rat discs. Inner anulus showed lesser localization. In clusters, both immuno-positive and -negative cells were present. Similar patterns of localization were seen in the sand rat specimens. Human disc cells in three-dimensional culture produced abundant TSP. CONCLUSIONS: The biologic basis for the avascular adult human disc does not appear to have been explored. Since TSP has recognized antiangiogenic effects both in vitro and in vivo, we suggest that the strong immunolocalization of TSP in the outer anulus indicates a role for TSP in the avascular status of the adult human and sand rat disc.

Adolescent↗
PubMed2005

Vertebral endplate architecture and vascularization: application of micro-computerized tomography, a vascular tracer, and immunocytochemistry in analyses of disc degeneration in the aging sand rat.

STUDY DESIGN: Lower lumbar vertebral endplates from young and old sand rats were assessed in an Institutional Animal Care and Use Committee approved study for architectural endplate features using micro-computerized tomography (CT) 3-dimensional (3D) models and vascularization studies by an in vivo vascular tracer or immunocytochemical identification of blood vessels. OBJECTIVE: To assess endplate porosity and vascularization using microCT architectural analysis, an in vivo vascular tracer, and immunocytochemical identification of blood vessels in the endplate. SUMMARY OF THE BACKGROUND DATA: The vertebral endplates, also called cartilage endplates, form the superior and inferior, or cranial and caudal, boundaries of the disc. In the human being and sand rat, the cartilaginous endplate undergoes calcification with aging and is replaced by bone. Endplate sclerosis has long been thought to play a role in disc degeneration by decreasing nutrient availability to the disc, but this is still poorly understood. Previous work has identified increasing bone mineral density with aging and disc degeneration in the sand rat model. METHODS: microCT models of the lower lumbar endplates of vertebrae at L5-6 and L6-7 were constructed from 6 younger (mean age 11 months) and 21 older (mean age 25.6 months) sand rats. Architectural features were scored on a semiquantitative scale for smoothness of the endplate face, irregularities on the endplate margin, and endplate thickness. There were 2 smaller sets of animals (n = 18) evaluated for endplate vascularity following in vivo injection of a fluorescent vascular tracer or by the use of immunocytochemistry to identify blood vessels. RESULTS: microCT revealed a solid bony surface to the endplate, which was not penetrated by vasculature; with aging/disc degeneration, there was roughening and pitting of the plate surface, and the development of irregular margins. In L5-6 and L6-7, sites of prominent disc degeneration evident on radiographs, the proportion of abnormalities in surface smoothness, margin irregularity, and endplate thickening were all statistically significant in both younger and older animals (P < or = 0.0027). More severe changes were evident in the caudal versus cranial endplate surfaces. Histologic study of vascular tracer showed that there was no penetration of the disc by vascular supply from the endplate; this was verified by immunocytochemical identification of blood vessels. The canal system within the endplate was a complex 3D interconnected network. CONCLUSIONS: Findings show that disc degeneration in the sand rat occurs concomitantly with marked architectural bony changes on the endplate face, including loss of smoothness and development of irregular bony margins. Vascular connections were not present between the endplate and disc; this was verified with microCT studies, in vivo vascular tracers, and traditional immunocytochemistry. The canal system within the imaged endplate was revealed to consist of a complex 3D interconnected network.

Aging↗
PubMed2005

Three-dimensional culture of human disc cells within agarose or a collagen sponge: assessment of proteoglycan production.

The objective of the present study was to assess proteoglycan production by human intervertebral disc cells cultured in vitro in selected cell carriers. Based on previous studies which evaluated disc cells seeded into collagen sponge, collagen gel, agarose, alginate or fibrin gel three-dimensional (3D) cell carriers, collagen sponge and agarose were found to provide superior microenvironments for formation of extracellular matrix (ECM). A standardized test design was used to evaluate ECM formed after 14 days of culture using the 1,9-dimethylmethylene blue (DMB) assay to assess sulfated glycosaminoglycan (S-GAG) production. Although agarose culture showed higher S-GAG levels compared to collagen sponge (2.94+/-2.20 (19) microg/ml S-GAG (mean+/-S.D. (n)) vs. 0.94+/-0.77 (22), respectively, p=0.0003), this is off-set by the significantly lower proliferation rate associated with culture of disc cells in agarose.

Adult↗
PubMed2005

Targeted deletion of the SPARC gene accelerates disc degeneration in the aging mouse.

SPARC (secreted protein, acidic, and rich in cysteine) is a matricellular protein that is present in the intervertebral disc; in man, levels of SPARC decrease with aging and degeneration. In this study, we asked whether targeted deletion of SPARC in the mouse influenced disc morphology. SPARC-null and wild-type (WT) mice were studied at 0.3-21 months of age. Radiologic examination of spines from 2-month-old SPARC-null mice revealed wedging, endplate calcification, and sclerosis, features absent in age-matched WT spines. Discs from 3-month-old SPARC-null mice had a greater number of annulus cells than those of WT animals (1884.6 +/- 397.9 [mean +/- SD] vs 1500.2 +/- 188.2, p=0.031). By 19 months discs from SPARC-null mice contained fewer cells than WT counterparts (1383.6 +/- 363.3 vs 1466.8 +/- 148.0, p=0.033). Histology of midsagittal spines showed herniations of lower lumbar discs of SPARC-null mice ages 14-19 months; in contrast, no herniations were seen in WT age-matched animals. Ultrastructural studies showed uniform collagen fibril diameters in the WT annulus, whereas in SPARC-null disc fibrils were of variable size with irregular margins. Consistent with the connective tissue deficits observed in other tissues of SPARC-null mice, our findings support a fundamental role for SPARC in the production, assembly, or maintenance of the disc extracellular matrix.

Aging↗
PubMed2005

The SOX9 transcription factor in the human disc: decreased immunolocalization with age and disc degeneration.

STUDY DESIGN: Human intervertebral disc anulus tissue was obtained in a prospective study of immunolocalization of SOX9, a protein that plays a role in chondrogenesis and Type II collagen expression. The Human Subjects Institutional Review Board approved experimental studies. Discs were obtained from surgical specimens and from control donors. OBJECTIVES: To determine whether SOX9 could be detected in discs of Thompson Grades I-IV using immunohistochemistry and to quantify the percentage of cells with SOX9 expression. SUMMARY OF BACKGROUND DATA: SOX9 is involved with cell-specific activation of COL2A1 in chondrocytes. Recent studies have used adenoviral delivery vectors expressing SOX9 to infect a chondroblastic cell line and human disc cells; SOX9 and Type II collagen production increased. The AdSOX9 virus has also been injected directly into rabbit discs in which disc architecture was preserved for 5 weeks. Despite current interest in SOX9 for gene therapy, there have been few studies of SOX9 in normal or degenerated discs. METHODS: Discs from 12 normal donors and 25 surgical subjects 15-76 years old were examined for SOX9 immunolocalization. Eight Thompson Grade I discs, 7 Grade II discs, 10 Grade III discs, and 12 Grade IV discs were studied. RESULTS: In Thompson Grade I discs, SOX9 was uniformly localized throughout the anulus and in some cells of the nucleus. However, in discs from adult donors, anulus cells were present that showed no SOX9 localization, although neighboring cells might be positive. Mean percent localization was 74% for Grade II discs, 69% for Grade III, and 71.6% for Grade IV. Cervical sites showed significantly greater localization than lumbar sites. CONCLUSIONS: Findings showed a uniform expression of SOX9 in the newborn healthy anulus. With aging and disc degeneration, some anulus cells no longer express this transcription product. These observations suggest that the loss of expression of SOX9 in some disc cells may play a role indisc aging and disc degeneration by resulting in decreased expression and production of Type II collagen.

Adolescent↗
PubMed2004

Cellular, but not matrix, immunolocalization of SPARC in the human intervertebral disc: decreasing localization with aging and disc degeneration.

STUDY DESIGN: Human intervertebral disc anulus tissue was obtained in a prospective study of immunolocalization of SPARC (secreted protein, acidic and rich in cysteine) (osteonectin). Experimental studies were approved by the authors' Human Subjects Institutional Review Board. Discs were obtained from surgical specimens and from control donors. OBJECTIVES: To determine whether SPARC could be detected in the disc with immunohistochemistry and to determine the incidence of SPARC-positive cells. SUMMARY OF THE BACKGROUND DATA: SPARC is a glycoprotein that has an important role in modulating interactions between cells and matrix. It influences remodeling, collagen fibrillogenesis, metalloproteinase expression, and cytokine expression. Little is known about SPARC in the disc, and one previous study reported the absence of its immunolocalization in fetal and adult disc tissue. METHODS: Eight normal human discs from subjects aged newborn to 10 years, and 11 disc specimens from control donors or surgical patients aged 15to 76 years were examined for immunolocalization of SPARC. Anulus cells were also tested for the presence of SPARC in vitro in monolayer or three-dimensional agarose culture. RESULTS: In discs of subjects aged newborn to 0.19 years, SPARC was present in all cells in the outer anulus, in 76.4% of inner anulus cells, and 76.0% of nucleus cells. Localization was significantly lower in anulus cells of study participants aged 4.7 to 76 years (66.7%, P = 0.04). Anulus cells cultured in agarose or monolayer showed positive localization in all cells. CONCLUSIONS: Findings show decreased presence of SPARC in disc cells of older subjects with disc degeneration and point to the importance of future studies designed to elucidate the unrecognized role of SPARC in disc remodeling, aging, and degeneration.

Adolescent↗
PubMed2004

Colony formation and matrix production by human anulus cells: modulation in three-dimensional culture.

STUDY DESIGN: Human intervertebral disc cells from the anulus were tested in a study of colony formation and extracellular matrix (ECM) production during long-term three-dimensional culture with exposure to selected cytokines. Experimental studies were approved by the authors' Human Subjects Institutional Review Board. OBJECTIVES: To quantitatively evaluate colony formation and qualitatively assess ECM production (using immunohistochemistry and in situ hybridization) in cells derived from Thompson Grades I to V discs and tested in culture with cytokines and nutrient supplementation. SUMMARY OF THE BACKGROUND DATA: Human intervertebral disc cells offer special in vitro challenges because of the slow-growing nature of these cells and their need for specialized three-dimensional in vitro conditions, which permit the expression and production of proteoglycans and Type II collagen, two ECM products that are important for disc cell biology. METHODS: Discs from 9 human subjects (2 control donors and 7 surgical patients, Thompson Grades I-V), mean age 35.8 years, were used to obtain anulus cells to be tested in three-dimensional agarose culture. Tests of specialized growth conditions included treatment with ITS (insulin-transferrin-sodium selenite supplement), insulin-like growth factor I (IGF-I), and transforming growth factor-beta1 (TGF-beta1). Cultures were evaluated after 14 to 36 days of culture for % colony formation and cell numbers/colony; immunocytochemistry, in situ hybridization, and quantitative histology were used to evaluate colony formation and ECM production. RESULTS: : Data showed that compared with the average 17.5% colony formation observed in controls, ITS, TGF-beta1 and ITS with IGF-I significantly increased colony formation (28.4%, 30.4%, and 30.4%, respectively, P < or = 0.04). Even cells derived from Thompson Grade V disc showed responsiveness to cytokines and improved production of ECM in vitro. CONCLUSIONS: : Findings indicated that cells derived from discs with advanced degeneration were still responsive to cytokines and could be modulated to produce Type II collagen and proteoglycans in three-dimensional culture by the addition of enriched media and selected cytokines. Such findings are important since they advance our understanding of how to modulate disc cell behavior in vitro, and may have application to potential future biologic therapies for disc degeneration.

Adult↗
PubMed2003

Bone mineral density of lumbar vertebral end plates in the aging male sand rat spine.

STUDY DESIGN: Lumbar vertebral segments from young and old male sand rats were assessed for quantitative determination of lumbar end plate bone mineral density. OBJECTIVES: To determine whether bone mineral density increases in the lumbar end plate with age in the male sand rat and to investigate its relationship to disc degeneration. SUMMARY OF THE BACKGROUND DATA: Few basic science studies evaluated the end plate and disc degeneration. The sand rat provides an excellent economical model in which disc degeneration is reliable and well characterized. METHODS: Bone mineral density data on cranial and caudal lumbar end plates of young (mean age 6.8 months) and old (mean age 23.3 months) male sand rats were assessed for changes related to age, lumbar position, and radiologic features. RESULTS: Mean bone mineral density was significantly greater in end plates in older compared to younger males (P <or= 0.0018). Mean end plate bone mineral density within young animals was not significantly different in levels L5 to L7; in old animals, bone mineral density was significantly different (greater) progressing from L5 to L7 (P < 0.0001). In older animals, mean end plate bone mineral density for each disc showed a significant increase with lower lumbar sites (P = 0.0068). Mean end plate bone mineral density was significantly greater in animals with radiographic evidence of disc wedging (P = 0.006). End plate bone mineral density correlated positively with age. CONCLUSIONS: Results provide quantitative bone mineral density data on end plate sclerosis in male sand rats. Data reveal site specificities and show that in old animals, end plate bone mineral density is greater than in young animals. Mean end plate bone mineral density was significantly greater at sites with radiographic disc wedging (P = 0.006). Data support the hypothesis that end plate sclerosis may play a role in disc degeneration.

Aging↗
PubMed2003

Computer aided vertebral visualization and analysis: a methodology using the sand rat, a small animal model of disc degeneration.

BACKGROUND: The purpose of this study is to present an automated system that analyzes digitized x-ray images of small animal spines identifying the effects of disc degeneration. The age-related disc and spine degeneration that occurs in the sand rat (Psammomys obesus) has previously been documented radiologically; selected representative radiographs with age-related changes were used here to develop computer-assisted vertebral visualization/analysis techniques. Techniques presented here have the potential to produce quantitative algorithms that create more accurate and informative measurements in a time efficient manner. METHODS: Signal and image processing techniques were applied to digitized spine x-ray images the spine was segmented, and orientation and curvature determined. The image was segmented based on orientation changes of the spine; edge detection was performed to define vertebral boundaries. Once vertebrae were identified, a number of measures were introduced and calculated to retrieve information on the vertebral separation/orientation and sclerosis. RESULTS: A method is described which produces computer-generated quantitative measurements of vertebrae and disc spaces. Six sand rat spine radiographs illustrate applications of this technique. Results showed that this method can successfully automate calculation and analysis of vertebral length, vertebral spacing, vertebral angle, and can score sclerosis. Techniques also provide quantitative means to explore the relation between age and vertebral shape. CONCLUSIONS: This method provides a computationally efficient system to analyze spinal changes during aging. Techniques can be used to automate the quantitative processing of vertebral radiographic images and may be applicable to human and other animal radiologic models of the aging/degenerating spine.

Aging↗
PubMed2003

Recent advances in disc cell biology.

STUDY DESIGN: There have been many advances over the past decade in understanding and experimentally modulating biologic aspects of intervertebral disc cell function. An overview of the current state of this biologic research is presented. OBJECTIVES: To provide clinicians with a review of important recent advances in biologic studies of the disc and their implications for potential disc therapies. SUMMARY OF BACKGROUND DATA: Historically, anatomic, biochemical, radiologic, and biomechanical studies of the intervertebral disc formed the foundation on which our understanding of disc function was built. Magnetic resonance imaging techniques that allowed viewing of soft tissue components of the disc further advanced imaging capabilities. METHODS: Recent publications are reviewed. RESULTS: Experimental approaches over the past decade have enabled researchers to look more critically at disc cell function. This is important because disc cell function produces the extracellular matrix components of the disc, which, in turn, shape the disc's subsequent physiologic and biomechanical functions. New approaches to the study of disc cell function, methods to manipulate disc cells, studies of intact discs and disc nutrition, vertebral endplate structure and function, tissue engineering, gene therapy, and the potential of stem cells in disc therapy are reviewed and discussed. CONCLUSIONS: Many believe that disc degeneration has a cellular basis. New research is helping us better understand healthy, aging, and degenerating discs. Modern methods to manipulate and modulate disc cell function open exciting and challenging new therapeutic possibilities for future biologic treatments of disc degeneration.

Animals↗
PubMed2003

Biologic strategies for the therapy of intervertebral disc degeneration.

Recent advances in tissue engineering have led to promising new approaches for the biologic treatment of disc degeneration. At present, there is no effective therapy for disc degeneration, a condition which results in large healthcare and socio-economic costs. This article will examine the current approaches used in biologic therapies for disc degeneration, including cell-based tissue engineering, gene therapy and the application of mesenchymal stem cells, and discuss their therapeutic potential, as demonstrated in animal models and experimental studies to date.

Animals↗
PubMed2002

Autologous intervertebral disc cell implantation: a model using Psammomys obesus, the sand rat.

STUDY DESIGN: Work presented here used a small animal model to illustrate the feasibility of autologous disc cell implantation. OBJECTIVES: To develop a small animal model for autologous disc cell implantation. SUMMARY OF THE BACKGROUND DATA: The use of autologous disc cells in the potential treatment of disc degeneration offers attractive possibilities for novel therapies. Results are presented on the use of the sand rat (Psammomys obesus), a small rodent that spontaneously develops disc degeneration during aging, in experimental studies in which cells were harvested from a lumbar intervertebral disc, expanded in monolayer tissue culture, labeled with agents that allow subsequent immunolocalization of these cells, and implanted in a second disc site of the donor animal. METHODS: Tissue culture, disc surgery, histology, and immunocytochemistry were used. Cells were either engrafted in a bioresorbable carrier tested for cell compatibility or injected into the recipient disc. Results were assessed with radiographic examination of the implantation site and with histology and immunocytochemistry. CONCLUSION: Data from 15 animals were obtained with engraftment resident in the animal for up to 33 weeks. Immunocytologic identification of engrafted cells showed that they integrated into the disc and were surrounded by normal matrix at time points up to 8 months postengraftment. Engrafted cells exhibited either a spindle-shaped morphology in the annulus or a rounded chondrocyte-like morphology in the nucleus. Although technically challenging, the authors' experience showed that autologous disc cell implantation can be successful and that the sand rat is a valuable model for autologous disc cell studies.

Animals↗
PubMed2002

Ultrastructure of the human intervertebral disc during aging and degeneration: comparison of surgical and control specimens.

STUDY DESIGN: Human intervertebral disc tissue from the annulus was obtained in a prospective study investigating the ultrastructural features of disc cells and extracellular matrix. Experimental studies were approved by the authors' Human Subjects Institutional Review Board. Discs were obtained from surgical specimens and control donors. OBJECTIVE: To compare the cellular and extracellular matrix characteristics of the annulus from control and surgical disc specimens using electron microscopy and specialized fixation that visualizes proteoglycans. SUMMARY OF THE BACKGROUND DATA: The ultrastructural features of disc cells and the disc matrix have received little attention, as compared with the literature on age- and disease-related changes in bone and cartilage. METHODS: Ultrastructural studies investigated disc tissue obtained from control and surgical disc specimens using transmission electron microscopy. Specialized fixation with ruthenium red was used to highlight matrix proteoglycans. RESULTS: Cellular and extracellular matrix fine structure was assessed in disc specimens from 29 control donors (newborns to 79-year-olds) and surgical disc specimens from 49 patients (16- to 77-year-olds). Control and surgical tissue showed similar ultrastructural features. Unusual matrix surrounding and encircling single cells or clusters of cells was common (48% of control and 63% of surgical specimens) and often contained fibrous long-spacing collagen (41.3% of control and 36.7% of surgical specimens). Ruthenium red greatly aided visualization of proteoglycans pooled in lacunar spaces. Variable cross-sectional diameters of collagen fibrils was present in 34% of control and 59% of surgical specimens. Regions with sparse interterritorial matrix were common. Cell morphology showed both cells with apoptotic nuclei and synthetically active cells that appeared healthy. CONCLUSIONS: Control and surgical specimens of the annulus showed similar ultrastructural features. Heterogeneity of collagen fibril diameter is an important observation because it is believed that fibril size relates to biomechanical disc function. Fibrous long-spacing collagen may reflect extracellular matrix remodeling or the presence of previous fibril depolymerization followed by repolymerization and reassociation with proteoglycans. Synthetic activity of disc cells is reflected in active rough endoplasmic reticulum, Golgi, and pools of proteoglycans in lacunar spaces and unusual extracellular matrix components that encircle cells and cell clusters. Such components may influence biomechanical quality. Departures from normal extracellular matrix organization of the aging or degenerating disc undoubtedly contribute to decreased biomechanical function of the annulus because they disrupt the normal annulus architecture. This study underscores the need for a fuller understanding of the dynamic relation between disc cells and the surrounding extracellular matrix, which they continually produce and remodel.

Adolescent↗
PubMed2002

Observations on morphologic changes in the aging and degenerating human disc: secondary collagen alterations.

BACKGROUND: In the annulus, collagen fibers that make up the lamellae have a wavy, planar crimped pattern. This crimping plays a role in disc biomechanical function by allowing collagen fibers to stretch during compression. The relationship between morphologic changes in the aging/degenerating disc and collagen crimping have not been explored. METHODS: Ultrastructural studies were performed on annulus tissue from 29 control (normal) donors (aged newborn to 79 years) and surgical specimens from 49 patients (aged 16 to 77 years). Light microscopy and specialized image analysis to visualize crimping was performed on additional control and surgical specimens. Human intervertebral disc tissue from the annulus was obtained in a prospective morphologic study of the annulus. Studies were approved by the authors' Human Subjects Institutional Review Board. RESULTS: Three types of morphologic changes were found to alter the crimping morphology of collagen: 1) encircling layers of unusual matrix disrupted the lamellar collagen architecture; 2) collagen fibers were reduced in amount, and 3) collagen was absent in regions with focal matrix loss. CONCLUSIONS: Although proteoglycan loss is well recognized as playing a role in the decreased shock absorber function of the aging/degenerating disc, collagen changes have received little attention. This study suggests that important stretch responses of collagen made possible by collagen crimping may be markedly altered by morphologic changes during aging/degeneration and may contribute to the early tissue changes involved in annular tears.

Journal Article↗
PubMed2002

The sand rat model for disc degeneration: radiologic characterization of age-related changes: cross-sectional and prospective analyses.

STUDY DESIGN: This report is composed of two studies, one cross-sectional and one prospective cohort study, that analyze the radiologic features of disc degeneration in the sand rat (Psammomys obesus). OBJECTIVES: To statistically assess progressive disc degeneration in this useful animal model in terms of a cross-sectional study and a prospective monthly evaluation of individual animals. SUMMARY OF BACKGROUND DATA: P. obesus is an attractive small rodent model for spontaneous age-related disc degeneration. Because disc degeneration is spontaneous, the model avoids use of chemonucleolysis or surgical injury to cause disc degeneration. Little is understood, however, about specific details of the progressive disc deterioration. METHODS: This study statistically assessed 158 animals in a cross-sectional study and 22 animals in a longitudinal study, which followed individual animals to 12 months of age. Radiologic features involving irregular disc margins, disc wedging, disc narrowing, endplate calcification, subchondral sclerosis, ligament calcification, and osteophyte formation were studied. RESULTS: Significant age-related cross-sectional changes were present for all features (P < or = 0.005). Males showed a statistically greater incidence of wedging at 6 and 12 months, wedging at 2 and 6 months, and endplate calcification at 2 months than did females. By 6 months of age, however, endplate calcification had a higher incidence in females than in males. Prospective analysis showed that wedging, narrowing, endplate calcification, and irregular disc margins were more common at 12 months of age than at 2 months (P = 0.0001). By the age of 12 months, all lumbar sites of both males and females showed endplate calcification and the majority of animals showed narrowing and wedging. CONCLUSIONS: Radiographic signs of degeneration were evident by age 2 months; wedging, narrowing, irregular disc margins, and endplate calcification were the most common degenerative changes in older animals. These data show that the sand rat provides a reliable, useful model of spontaneous disc degeneration.

Aging↗
PubMed2002

Expression and localization of estrogen receptor-beta in annulus cells of the human intervertebral disc and the mitogenic effect of 17-beta-estradiol in vitro.

BACKGROUND: Recent evidence suggests that estrogens exert effects in different tissues throughout the body, and that the estrogen receptor beta (ERbeta) may be important for the action of estrogen (17-beta-estradiol) on the skeleton. The cellular localization of ERbeta in the human intervertebral disc, however, has not yet been explored. METHODS: Human disc tissue and cultured human disc cells were used for immunocytochemical localization of ERbeta. mRNA was isolated from cultured human disc cells, and RT-PCR amplification of ERbeta was employed to document molecular expression of this receptor. Cultured human disc cells were tested to determine if 17-beta-estradiol stimulated cell proliferation. RESULTS: In this report data are presented which provide evidence for ERbeta gene expression in human intervertebral disc cells in vivo and in vitro. Culture of annulus cells in the presence of 10-7 M 17-beta-estradiol significantly increased cell proliferation. CONCLUSIONS: These data provide new insight into the biology of cells in the annulus of the intervertebral disc.

Journal Article↗