Biomedical subjects

T Aigner

Publications and source records attributed to T Aigner.

At least 19 recordsLinked to original sources

PubMed2005

Increase in degraded collagen type II in synovial fluid early in the rabbit meniscectomy model of osteoarthritis.

OBJECTIVE: The objective of this study was to determine whether collagen type II breakdown products in synovial fluid (SF), detected by an enzyme-linked immunoassay, represent a useful marker for early events in osteoarthritis (OA) in the rabbit medial meniscectomy model. DESIGN: Complete medial meniscectomy was performed on the right knee joints of 32 rabbits. Balanced groups of rabbits were then sacrificed at 2, 4, 8, and 12 weeks post-surgery. An additional 8 unoperated and 11 sham-operated animals served as controls. SF lavages were performed on right and left knee joints of the same animals at sacrifice. The proteolytic epitope of type II collagen was monitored using an enzyme-linked immunoassay. RESULTS: Macroscopically visible surface fibrillation and focal erosions appeared as early as 2 weeks after meniscectomy in the femorotibial joint (P<0.01). OA developed gradually during the later observation period, and then predominantly on the medial tibial plateau and medial femur. Significant histological alterations in cartilage, including a loss of proteoglycans, surface irregularities, and clefts, were detected at 2 weeks after meniscectomy (P<0.01). Collagen type II epitope levels in SF lavage samples were elevated peaking at 2 weeks after meniscectomy (P<0.02). Levels decreased at later time points, but they were still raised at 12 weeks (P< or =0.05). Highly significant correlations were found between the SF collagen type II epitope levels and the macroscopic and microscopic scoring results (Spearman rho correlation coefficient, macroscopy-collagen type II epitope r=0.222, P=0.025; microscopy-collagen type II epitope r=0.436, P< or =0.01). CONCLUSION: In this rabbit model of medial meniscectomy, levels of type II collagen fragments in SF appear to provide a useful marker of the early degenerative changes.

Animals↗

PubMed2005

Oxygen and reactive oxygen species in cartilage degradation: friends or foes?

OBJECTIVES: This review is focused on the influence of oxygen and derived reactive species on chondrocytes aging, metabolic function and chondrogenic phenotype. METHODS: A systematic computer-aided search of the Medline database. RESULTS: Articular cartilage is an avascular tissue, and consequently oxygen supply is reduced. Although the basal metabolic functions of the cells are well adapted to hypoxia, the chondrocyte phenotype seems to be oxygen sensitive. In vitro, hypoxia promotes the expression of the chondrogenic phenotype and cartilage-specific matrix formation, indicating that oxygen tension is probably a key parameter in chondrocyte culture, and particularly in the context of tissue engineering and stem cells transplantation. Besides the influence of oxygen itself, reactive oxygen species (ROS) play a crucial role in the regulation of a number of basic chondrocyte activities such as cell activation, proliferation and matrix remodeling. However, when ROS production exceeds the antioxidant capacities of the cell, an "oxidative stress" occurs leading to structural and functional cartilage damages like cell death and matrix degradation. CONCLUSIONS: This paper is an overview of the in vitro and in vivo studies published on the influence of oxygen and derived reactive species on chondrocyte aging, metabolic function, and the chondrogenic phenotype. It shows, that oxygen and ROS play a crucial role in the control of cartilage homeostasis and that at this time, the exact role of "oxidative stress" in cartilage degradation still remains questionable.

Aging↗

PubMed2005

Comparison of the chondrosarcoma cell line SW1353 with primary human adult articular chondrocytes with regard to their gene expression profile and reactivity to IL-1beta.

OBJECTIVE: In this study, the human chondrosarcoma cell line SW1353 was investigated by gene expression analysis in order to validate it as an in vitro model for primary human (adult articular) chondrocytes (PHCs). METHODS: PHCs and SW1353 cells were cultured as high density monolayer cultures with and without 1ng/ml interleukin-1beta (IL-1beta). RNA was isolated and assayed using a custom-made oligonucleotide microarray representing 312 chondrocyte-relevant genes. The expression levels of selected genes were confirmed by real-time polymerase chain reaction and the gene expression profiles of the two cell types, both with and without IL-1beta treatment, were compared. RESULTS: Overall, gene expression profiling showed only very limited similarities between SW1353 cells and PHCs at the transcriptional level. Similarities were predominantly seen with respect to catabolic effects after IL-1beta treatment. In both cell systems matrix metalloproteinase-1 (MMP-1), MMP-3 and MMP-13 were strongly induced by IL-1beta, without significant induction of MMP-2. IL-6 was also found to be up-regulated by IL-1beta in both cellular models. On the other hand, intercellular mediators such as leukemia inhibitory factor (LIF) and bone morphogenetic protein-2 (BMP-2) were not induced by IL-1beta in SW1353 cells, but significantly up-regulated in PHCs. Bioinformatical analysis identified nuclear factor kappa-B (NFkappaB) as a common transcriptional regulator of IL-1beta induced genes in both SW1353 cells and PHCs, whereas other transcription factors were only found to be relevant for individual cell systems. CONCLUSION: Our data characterize SW1353 cells as a cell line with only a very limited potential to mimic PHCs, though SW1353 cells can be of value to study the induction of protease expression within cells, a phenomenon also seen in chondrocytes.

Aged↗

PubMed2005

DNA methylation is not likely to be responsible for aggrecan down regulation in aged or osteoarthritic cartilage.

BACKGROUND: Expression of aggrecan is reduced during aging and osteoarthritic cartilage degeneration. CpG methylation may have a role in the down regulation of aggrecan transcriptions. OBJECTIVE: To investigate whether a correlation between gene methylation and expression of aggrecan in chondrocytes exists. METHODS: The human aggrecan promoter region was analysed computationally for CpG-rich regions. These were investigated for the methylation of C residues in normal (aged) and osteoarthritic chondrocytes by the bisulphite method for modifying DNA as well as sequence analysis using DNA directly extracted from normal and osteoarthritic cartilage tissue. Additionally, chondrocytic cell lines were investigated for methylation within the aggrecan promoter region. RESULTS: The CpG-rich promoter region of the human aggrecan gene contains a 0.6 kb region that meets the criteria of a CpG island as defined by prediction programmes. A significant correlation of aggrecan mRNA expression levels and methylation status in normal (aged) and osteoarthritic chondrocytes as well as in different chondrocytic cell lines was not found. CONCLUSIONS: Expression of aggrecan in normal cartilage and diseased states is not modulated by gross changes of CpG methylation of its promoter region. CpG methylation does not have a central role in the switch off of aggrecan promoter activity in human adult articular chondrocytes.

Aged↗

PubMed2004

Phenotypic characterization of chondrosarcoma-derived cell lines.

Gene expression profiling of three chondrosarcoma derived cell lines (AD, SM, 105KC) showed an increased proliferative activity and a reduced expression of chondrocytic-typical matrix products compared to primary chondrocytes. The incapability to maintain an adequate matrix synthesis as well as a notable proliferative activity at the same time is comparable to neoplastic chondrosarcoma cells in vivo which cease largely cartilage matrix formation as soon as their proliferative activity increases. Thus, the investigated cell lines are of limited value as substitute of primary chondrocytes but might have a much higher potential to investigate the behavior of neoplastic chondrocytes, i.e. chondrosarcoma biology.

Cell Culture Techniques↗

PubMed2004

Molecular phenotyping of HCS-2/8 cells as an in vitro model of human chondrocytes.

OBJECTIVE: Cultures of primary articular chondrocytes for studying chondrocyte biology are notoriously difficult to handle. One alternative is the use of chondrocytic cell lines. Because the HCS-2/8 cells are the most widely used cell line in cartilage research, we investigated the molecular phenotype of these cells by mRNA-expression profiling. DESIGN: Monolayers of HCS-2/8 cells were cultured to sub-confluence, confluence and over-confluence; primary human chondrocytes were grown in monolayer culture and alginate-bead cultures and several other chondrocytic cell lines were cultured as monolayers. RNA was isolated and analyzed by cDNA array profiling using Affymetrix GeneChips (U95A/U95Av2) and quantitative PCR. RESULTS: Important similarities, but also remarkable differences between the HCS-2/8 cells and adult human articular chondrocytes were detected: Aggrecan and several cartilage typical collagens as well as SOX9 transcripts were strongly expressed in HCS-2/8 cells, whereas HCS-2/8 cells expressed hardly any chondrocyte-typical cartilage matrix degrading enzymes. Of all culturing conditions, clustering analysis showed that HCS-2/8 cultured at confluence are most closely related to primary chondrocytes. CONCLUSION: Our study confirms how careful one needs to be in choosing in vitro model systems for investigating effects of interest. The major issue of chondrocyte cell lines appears to be that they mainly proliferate and show less expression of genes of matrix synthesis and turnover. A successful approach will have to select suitable chondrocyte cell lines and to validate findings obtained using primary chondrocytes. This allows to establish a reproducible in vitro model showing the property of interest and subsequently to relate back the obtained results to the physiologic situation.

Adult↗

PubMed2004

Chondroptosis: a variant of apoptotic cell death in chondrocytes?

Evidence has accumulated in recent years that programmed cell death (PCD) is not necessarily synonymous with the classical apoptosis, as defined by Kerr and Wyllie, but that cells use a variety of pathways to undergo cell death, which are reflected by different morphologies. Although chondrocytes with the hallmark features of classical apoptosis have been demonstrated in culture, such cells are extremely rare in vivo. The present review focuses on the morphological differences between dying chondrocytes and classical apoptotic cells. We propose the term 'chondroptosis' to reflect the fact that such cells are undergoing apoptosis in a non-classical manner that appears to be typical of programmed chondrocyte death in vivo. Unlike classical apoptosis, chondroptosis involves an initial increase in the endoplasmic reticulum and Golgi apparatus, reflecting an increase in protein synthesis. The increased ER membranes also segment the cytoplasm and provide compartments within which cytoplasm and organelles are digested. In addition, destruction occurs within autophagic vacuoles and cell remnants are blebbed into the lacunae. Together these processes lead to complete self-destruction of the chondrocyte as evidenced by the presence of empty lacunae. It is speculated that the endoplasmic reticulum pathway of apoptosis plays a greater role in chondroptosis than receptor-mediated or mitochondrial pathways and that lysosomal proteases are at least as important as caspases. Because chondroptosis does not depend on phagocytosis, it may be more advantageous in vivo, where chondrocytes are isolated within their lacunae. At present the initiation factors or the molecular pathways involved in chondroptosis remain unclear.

Animals↗

PubMed2004

Mesenchymal chondrosarcoma: an immunohistochemical study of 10 cases examining prognostic significance of proliferative activity and cellular differentiation.

AIMS: Mesenchymal chondrosarcoma is a rare malignant chondrogenic neoplasm that tends to affect young adults and teenagers. The prognosis is unpredictable, and the identification of prognostic markers that could aid in determining the behaviour of this tumour would be helpful. There are few studies in the literature that have attempted to address this issue. METHODS AND RESULTS: In this study, we explored the prognostic significance of three different parameters: (1) tissue morphology of small cell areas, (2) the expression of tumour differentiation marker genes, and (3) the proliferation rate. Our results did not show a correlation of prognosis with the histological features of the neoplastic small cell areas or the expression of tumour differentiation genes. However, the proliferative activity of the tumour cells appeared to have some prognostic significance as related to patient survival. CONCLUSION: Mesenchymal chondrosarcoma is a rare tumour with a wide clinical range of behaviour. Therefore, it is difficult to obtain reliable prognostic parameters. Nevertheless, our study suggests that proliferative activity may be a useful prognostic parameter for mesenchymal chondrosarcomas.

Adolescent↗

PubMed2004

Aging theories of primary osteoarthritis: from epidemiology to molecular biology.

Osteoarthritis is the most common disabling condition of humans in the western world. It has been known for a very long time that aging is the most prominent risk factor for the initiation and progression of the disease, but the explanations for this phenomenon have changed over time. The most longstanding theory is that osteoarthritis develops because of continuous mechanical wear and tear. However, osteoarthritis can also be the result of time/age-related modifications to cartilage matrix components. One of the simplest biological explanations for the initiation and progression of osteoarthritic cartilage degeneration is a mere loss of viable cells, due to apoptosis or other mechanisms. Overall, the most likely scenario is that the cells and the matrix of articular cartilage get older over time, and eventually the tissue enters a senescence-like state that makes it more prone to enter the osteoarthritic degeneration pathway. Thus, patients with osteoarthritis might progress more quickly to the senescence phenotype compared to others. Moreover, stressful conditions associated with the osteoarthritic disease process might further promote chondrocyte senescence. Primary osteoarthritis in this model would be a "premature" degeneration of the joint due to a premature chondrocyte senescence. By analogy to neurodegenerative disorders, one could refer to osteoarthritis as the "M. Alzheimer" of articular cartilage. One of the most important implications of this hypothesis is that it points to issues of cellular degeneration as the basis for understanding the initiation and progression of osteoarthritis. Equally important, it emphasizes that whatever treatment we envisage for osteoarthritis, we must take into account that we are dealing with aged/(pre)senescent cells that no longer have the ability of their juvenile counterparts to counteract the many mechanical, inflammatory, and/or other assaults to the tissue.

Aging↗

PubMed2004

Comparative analysis of imbalances in genomic DNA and mRNA expression levels in chondrosarcoma-derived cell line FSCP-1.

Malignant cell transformation results from multiple biological alterations including chromosomal abnormalities, oncogene activation, loss of suppressor gene function and a imbalance in cell regulating processes. The aim of our study was to combine gene expression and genomic analysis to evaluate the cellular phenotype of a chondrosarcoma cell line, which is potentially a useful in vitro model system for physiological and/or neoplastic chondrocytes. cDNA-array, quantitative PCR and comparative genomic hybridization (CGH) technologies were used to analyze gene expression profiles of chondrosarcoma cell line FSCP-1 in correlation to changes of DNA copy number on corresponding chromosomal sections. Gene expression analysis revealed similarities, but also great differences in between the chondrosarcoma cell line and physiological chondrocytes. In particular the proliferative activity was up-regulated and molecules involved in matrix synthesis and turnover down-regulated. CGH analysis revealed a heterogeneous pattern of DNA gains or losses. The c-myc oncogene, located on 8q24.12-q24.13, was the only gene with a marked up-regulation located on a chromosome section with a gain of DNA copy number. The inability of the chondrosarcoma cell line FSCP-1 to maintain an adequate matrix turnover as well as a notable proliferative activity is similar to neoplastic chondrosarcoma in vivo. The limited correlation between the CGH analysis and the gene expression pattern supports the notion that also in neoplastic cells most genes are not primarily regulated by the gene dosage, but by cellular regulation pathways. However, genes such as c-myc might represent significant exceptions potentially relevant for the clinico-biological behavior of the neoplasms.

Bone Neoplasms↗

PubMed2003

Collagens--structure, function, and biosynthesis.

The extracellular matrix represents a complex alloy of variable members of diverse protein families defining structural integrity and various physiological functions. The most abundant family is the collagens with more than 20 different collagen types identified so far. Collagens are centrally involved in the formation of fibrillar and microfibrillar networks of the extracellular matrix, basement membranes as well as other structures of the extracellular matrix. This review focuses on the distribution and function of various collagen types in different tissues. It introduces their basic structural subunits and points out major steps in the biosynthesis and supramolecular processing of fibrillar collagens as prototypical members of this protein family. A final outlook indicates the importance of different collagen types not only for the understanding of collagen-related diseases, but also as a basis for the therapeutical use of members of this protein family discussed in other chapters of this issue.

Collagen↗

PubMed2003

Collagens--major component of the physiological cartilage matrix, major target of cartilage degeneration, major tool in cartilage repair.

Collagens serve important mechanical functions throughout the body and in particular in the connective tissues. Additionally, collagens exert important functions as cellular microenvironment and partly via binding and release of cellular growth mediators. In articular cartilage, fibrillar collagens are providing most of the biomechanical properties of the extracellular matrix essential for its functioning. The collagenous matrix is one main target of destructive processes in general degenerative joint disease and focal matrix lesions. The development of an adequate collagen framework represents the major aim of therapeutic cartilage repair. In this respect, collagenous matrices or collagen-imitating scaffolds are more and more emerging as highly suitable vehicles for cell and (growth) factor transport into cartilage lesion. Thus, collagens are not only major constituents of connective tissues in terms of integrity and function, they are also major targets of tissue destruction and regeneration and might become major tools to achieve tissue repair.

Absorbable Implants↗

PubMed2003

[Allergy-associated colitis. Characterization of an entity and its differential diagnoses].

There is substantial evidence that allergic reactions exist in the gastrointestinal tract (GI). However, patients with food allergy-related enteropathy pose a diagnostic challenge to physicians because the clinical features are variable, unspecific, occur in other gastrointestinal disorders, and specific diagnostic tools are missing. Several recent studies and reviews have focused on the function of eosinophilic granulocytes in GI disease. The role of eosinophils in the pathophysiology of GI hypersensitivity reactions is poorly defined. However, some findings have been reported that imply an involvement of eosinophils in allergic reactions of the gut. The presumptive histology of allergy-associated colitis in colonic and ileal biopsies is based on prominent pure eosinophilic infiltration of a normal lamina propria, submucosa and epithelium with variable degrees of degranulation. An immunoperoxidase stain for eosinophilic peroxidase is supportive in establishing the diagnosis if suspected. Neutrophils or mononuclear infiltrates are not significantly increased and damage to the intestinal tissue is not prominent. Despite characteristic histologic changes in colonic biopsy specimens, a final diagnosis depends on careful clinical examination and exclusion of several differential diagnoses.

Colitis↗

PubMed2003

Molecular phenotyping of human chondrocyte cell lines T/C-28a2, T/C-28a4, and C-28/I2.

OBJECTIVE: Because the immortalized chondrocyte cell lines C-28/I2, T/C-28a2, and T/C-28a4 have become a common tool in cartilage research, permitting investigations in a largely unlimited and standardized manner, we investigated the molecular phenotype of these cell lines by gene expression profiling. METHODS: Complementary DNA-array analysis as well as online quantitative polymerase chain reaction were used to identify the gene expression profiles of the 3 cell lines cultured in monolayer and alginate beads, as compared with the expression profiles of cultured human adult primary chondrocytes. RESULTS: A similar, but not identical, gene expression profile was established for all 3 cell lines. SOX9 was expressed at a significant level in all 3 cell lines. Extracellular matrix proteins and matrix-degrading proteases were rarely expressed. In contrast, genes involved in the cell cycle were strongly up-regulated, as compared with the expression levels in physiologic chondrocytes. CONCLUSION: The expression of SOX9, the master gene of chondrocytic cell differentiation, reflects the basically chondrocytic phenotype of these cells. However, the major issue appears to be that these cell lines mainly proliferate and show less expression of genes involved in matrix synthesis and turnover. In this respect, C-28/I2 cells display the highest levels of matrix-anabolic and matrix-catabolic genes and thus are presumably preferable for use in investigating chondrocyte anabolic and catabolic activity and its regulation. None of the 3 cell lines appears to be a direct substitute for primary chondrocytes. A successful approach will have to validate the findings obtained with chondrocyte cell lines by using primary chondrocytes or cartilage-tissue cultures. This would permit the establishment of reproducible in vitro models and subsequently allow investigators to relate the findings to the physiologic situation.

Adult↗

PubMed2003

Osteophyte development--molecular characterization of differentiation stages.

OBJECTIVE: Osteophytes are non-neoplastic osteo-cartilaginous protrusions growing at the margins of osteoarthritic joints. They can not only be considered as in situ repair tissue, but also represent an excellent in vivo model for induced cartilage repair processes. Our focus was to identify different steps of osteophyte development via analysis of expression patterns of marker genes of chondrocytic differentiation. DESIGN: We performed an extensive analysis of the presence and expression of matrix components using histochemical, immunohistochemical and in situ hybridization technology. RESULTS: Four different stages of osteophyte formation could be identified based on histomorphological and cell biological parameters: starting from mesenchymal condensates, chondrogenic differentiation is indicated by the onset of Col2A and aggrecan expression (stage I). Stage II shows fibrocartilage with an admixture of cartilaginous and fibrous matrix components such as Col2 and aggrecan on the one hand and Col1 on the other hand. The proliferating osteophyte (stage III) shows a zonal organization similar to the fetal growth plate cartilage with extensive chondrocyte hypertrophy in the zones next to ongoing endochondral bone formation. 'Mature' osteophytes (stage IV) resembled largely articular hyaline cartilage with a predominance of Col2 and aggrecan and Col6 found mainly pericellularily. CONCLUSIONS: The development of osteophytes is a good in vivo model to pursue chondrocyte differentiation from pluripotent mesenchymal cells to mature or hypertrophic chondrocytes in situ in the adult. The analysis of marker molecules of mesenchymal differentiation allows to identify different stages of repair tissue development and the transformation from fibrous tissue to neo-cartilage. Tissue architecture and matrix composition in mature osteophytes suggests that metaplastic neo-cartilagenous tissue might be one potential source of cartilage repair tissue in the adult joint.

Aged↗

PubMed2003

YKL-39 (chitinase 3-like protein 2), but not YKL-40 (chitinase 3-like protein 1), is up regulated in osteoarthritic chondrocytes.

OBJECTIVE: To investigate quantitatively the mRNA expression levels of YKL-40, an established marker of rheumatoid and osteoarthritic cartilage degeneration in synovial fluid and serum, and a closely related molecule YKL-39, in articular chondrocytes. METHODS: cDNA array and online quantitative polymerase chain reaction (PCR) were used to measure mRNA expression levels of YKL-39 and YKL-40 in chondrocytes in normal, early degenerative, and late stage osteoarthritic cartilage samples. RESULTS: Expression analysis showed high levels of both proteins in normal articular chondrocytes, with lower levels of YKL-39 than YKL-40. Whereas YKL-40 was significantly down regulated in late stage osteoarthritic chondrocytes, YKL-39 was significantly up regulated. In vitro both YKLs were down regulated by interleukin 1beta. CONCLUSIONS: The up regulation of YKL-39 in osteoarthritic cartilage suggests that YKL-39 may be a more accurate marker of chondrocyte activation than YKL-40, although it has yet to be established as a suitable marker in synovial fluid and serum. The decreased expression of YKL-40 by osteoarthritic chondrocytes is surprising as increased levels have been reported in rheumatoid and osteoarthritic synovial fluid, where it may derive from activated synovial cells or osteophytic tissue or by increased matrix destruction in the osteoarthritic joint. YKL-39 and YKL-40 are potentially interesting marker molecules for arthritic joint disease because they are abundantly expressed by both normal and osteoarthritic chondrocytes.

Adipokines↗

PubMed2003

Autologous chondrocyte implantation and osteochondral cylinder transplantation in cartilage repair of the knee joint. A prospective, comparative trial.

BACKGROUND: Current methods used to restore the joint surface in patients with localized articular cartilage defects include transplantation of an autologous osteochondral cylinder and implantation of autologous chondrocytes. The purpose of this study was to evaluate the clinical and histological outcomes of these two techniques. METHODS: We performed a prospective clinical study to investigate the two-year outcomes in forty patients with an articular cartilage lesion of the femoral condyle who had been randomly treated with either transplantation of an autologous osteochondral cylinder or implantation of autologous chondrocytes. Biopsy specimens from representative patients of both groups were evaluated with histological staining, immunohistochemistry, and scanning electron microscopy. RESULTS: According to the postoperative Lysholm score, the recovery after autologous chondrocyte implantation was slower than that after osteochondral transplantation at six months (p < or = 0.015), twelve months (p < or = 0.001), and twenty-four months (p < or = 0.012). On the basis of the Meyers score and the Tegner activity score, the results were equally good with the two methods two years after treatment. Histomorphological evaluation of biopsy specimens within two years after autologous chondrocyte implantation demonstrated a complete, mechanically stable resurfacing of the defect in all patients. The tissue consisted mainly of fibrocartilage, while localized areas of hyaline-like regenerative cartilage could be detected close to the subchondral bone. Although a gap remained at the site of the transplantation in all five biopsy specimens examined as long as two years after osteochondral cylinder transplantation, histomorphological analysis and scanning electron microscopy revealed no differences between the osteochondral transplants and the surrounding original cartilage. CONCLUSIONS: Both treatments resulted in a decrease in symptoms. However, the improvement provided by the autologous chondrocyte implantation lagged behind that provided by the osteochondral cylinder transplantation. Histologically, the defects treated with autologous chondrocyte implantation were primarily filled with fibrocartilage, whereas the osteochondral cylinder transplants retained their hyaline character, although there was a persistent interface between the transplant and the surrounding original cartilage. Limitations of our study included the small number of patients, the relatively short (two-year) follow-up, and the absence of a control group.

Adolescent↗

PubMed2002

Towards a new understanding and classification of chondrogenic neoplasias of the skeleton--biochemistry and cell biology of chondrosarcoma and its variants.

Despite substantial knowledge on the clinicopathology of chondrogenic skeletal neoplasms, only limited insights into the biology of the different tumor variants are available. There are virtually no established molecular markers for identification and classification of these neoplasms. In this paper, we present a systematic review of the biochemistry and cell biology of chondrogenic neoplasms of the bone focussing on our own recent investigations. The hallmark of all differentiated chondrogenic tumors is the presence of neoplastic chondrocytic cells responsible for the formation of the characteristic cartilaginous tumor matrix. These cells can show the full differentiation potential of physiologic chondrocytes depending on the tumor entity investigated. The high phenotypic diversity of physiologic chondrocytes explains the previously poorly understood, striking heterogeneity of the neoplastic cells and their surrounding extracellular matrix not only between different but also within chondrogenic tumors. In our studies, tumor classifications, so far based only on histomorphological criteria, were either confirmed or corrected: mesenchymal chondrosarcomas represent the prototypic neoplasm of pre-chondrogenic undifferentiated cells undergoing multifocal chondrocytic differentiation. Enchondromas, osteochondromas, and conventional chondrosarcomas are neoplasms of multi-phenotypically differentiated chondrocytes. Clear cell chondrosarcomas appear to be neoplasms of hypertrophic chondrocytic cells. A peculiar biology is displayed by dedifferentiated chondrosarcomas, which at least in most cases show neither "anaplasia" nor "dedifferentiation", but most likely "transdifferentiation" of part of the neoplastic cells to a cellular phenotype of a different mesenchymal differentiation lineage. Chondroblastomas do not show any chondroblastic differentiation at all. Our studies delineate molecular markers of chondrogenic neoplasms of the skeleton, which have the potential to be the basis of a new biology-orientated classification of skeletal neoplasms. The expression analysis of extracellular matrix genes, in particular of the collagen types, might be able to play herein a leading role in classification and diagnosis, similar to the cytokeratin subtypes or the CDs (cluster of differentiation) for the classification and diagnosis of neoplasms of the epithelia and the lymphatics.

Animals↗