Identification of molecular markers for articular cartilage

Hissnauer, Tim N.; Baranowsky, Anke; Pestka, Jan M.; Streichert, Thomas; Wiegandt, Katharina; Goepfert, Christine; Beil, Frank Timo; Albers, Joachim; Schulze, Jochen; Ueblacker, Peter; Petersen, J.; Schinke, Thorsten; Meenen, N. M.; Pörtner, Ralf; Amling, Michael

doi:10.1016/j.joca.2010.10.002

Cited by 38 publications

(41 citation statements)

References 32 publications

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“…Previous gene profiling studies also showed higher expressions of these factors including Dkk3, Wif1, Sfrp5, Igfbp4/5, Nov, Gdf10, Grem1 and Frzb in articular chondrocytes than growth plate chondrocytes (9,13,18). We speculate that it may be more appropriate to use these signaling molecules in tissue engineering of articular cartilage because the articular chondrocytes under their physiological conditions in vivo are exposed to these factors and therefore may respond to them more optimally.…”

Section: Discussionmentioning

confidence: 58%

“…Esm1 has been reported to be secreted mainly by endothelial cells of organs like lung or kidney and to function as a regulator of cell adhesion, inflammatory disorders, and tumor progression (19,20). Similarly, Thbs4 is another extracellular matrix protein holding promise for the study of the role of articular cartilage integrity in the 16 selected genes because Thbs4 was also reported to show the highest specificity for articular cartilage expression in a previous RT-PCR screening (18). In fact, most of the other thrombospon- A, effects of rhFGF18 on mRNA levels of Mmp, Adamts, and Timp family genes after 3-day culture of mouse femoral heads (2 g/ml rhFGF18) and 1-day culture of mouse articular chondrocytes (250 ng/ml rhFGF18).…”

Section: Discussionmentioning

confidence: 99%

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Identification of Fibroblast Growth Factor-18 as a Molecule to Protect Adult Articular Cartilage by Gene Expression Profiling

Mori¹,

Saito

Chang

et al. 2014

Journal of Biological Chemistry

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Background: Prevention of adult articular cartilage and treatment of its lesions are essential. Results: Microarray analyses identified Fgf18, which inhibits aggrecan release from cartilage and enhances proliferation of chondrocytes. The intra-articular injection of rhFGF18 prevented cartilage degeneration in a rat osteoarthritis model. Conclusion: Fgf18 protects adult articular cartilage through Timp1 expression. Significance: Fgf18 may represent a therapeutic agent for osteoarthritis.

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Section: Discussionmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 99%

Identification of Fibroblast Growth Factor-18 as a Molecule to Protect Adult Articular Cartilage by Gene Expression Profiling

Mori¹,

Saito

Chang

et al. 2014

Journal of Biological Chemistry

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“…n-3 PUFAs inhibit these pathways directly through ligand-mediated activation of GPR120 and downstream inactivation of transforming growth factor-β activated kinase 1 (TAK1) 13 . Chondrocytes express GPR120 39 , but the physiological relevance of GPR120-mediated inactivation of TAK1 in articular chondrocytes is unknown.…”

Section: Discussionmentioning

confidence: 99%

Metabolic enrichment of omega-3 polyunsaturated fatty acids does not reduce the onset of idiopathic knee osteoarthritis in mice

Cai

Hutchison

Hudson

et al. 2014

Osteoarthritis and Cartilage

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Objective We evaluated the effect of a reduction in the systemic ratio of n-6:n-3 polyunsaturated fatty acids (PUFAs) on changes in inflammation, glucose metabolism, and the idiopathic development of knee osteoarthritis (OA) in mice. We hypothesized that a lower ratio of n-6:n-3 PUFAs would protect against OA markers in cartilage and synovium, but not bone. Design Male and female fat-1 transgenic mice (Fat-1), which convert dietary n-6 to n-3 PUFAs endogenously, and their wild-type (WT) littermates were fed an n-6 PUFA enriched diet for 9-14 months. The effect of gender and genotype on serum PUFAs, IL-6, TNF-α, and glucose tolerance was tested by 2-factor analysis of variance. Cortical and trabecular subchondral bone changes were documented by micro-focal computed tomography, and knee OA was assessed by semi-quantitative histomorphometry grading. Results The n-6:n-3 ratio was reduced 12-fold and 7-fold in male and female Fat-1 mice, respectively, compared to WT littermates. IL-6 and TNF-α levels were reduced modestly in Fat-1 mice. However, these systemic changes did not reduce osteophyte development, synovial hyperplasia, or cartilage degeneration. Also the fat-1 transgene did not alter subchondral cortical or trabecular bone morphology or bone mineral density. Conclusions Reducing the systemic n-6:n-3 ratio does not slow idiopathic changes in cartilage, synovium, or bone associated with early-stage knee OA in mice. The anti-inflammatory and anti-catabolic effects of n-3 PUFAs previously reported for cartilage may be more evident at later stages of disease or in post-traumatic and other inflammatory models of OA.

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“…Development and grading of OA is mainly determined by histological analyses [4,6,14]. In humans, grade and prevalence of OA may be detected by MRI scanning [15,16] and through X-ray examination [17]. Thus, correlation of histological changes and MRI scanning is needed in diagnosis of OA.…”

Section: Introductionmentioning

confidence: 99%

“…The pig and notably the Göttingen Minipig (GM) is often used in articular cartilage research [5,17,23,24] and is also a common model for the study of regeneration of focal cartilage defects [7,25,26] but the transection of the ACL has rarely been performed in this species up to now [6]. For the articular cartilage research skeletal mature individuals are required as older pigs may mirror the human condition better, as OA is mostly an affliction of older people whether or not there were previous injuries [27,28].…”

Section: Introductionmentioning

confidence: 99%

Osteoarthritis in the Knee Joints of Göttingen Minipigs after Resection of the Anterior Cruciate Ligament? Missing Correlation of MRI, Gene and Protein Expression with Histological Scoring

et al. 2016

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IntroductionThe Göttingen Minipig (GM) is used as large animal model in articular cartilage research. The aim of the study was to introduce osteoarthritis (OA) in the GM by resecting the anterior cruciate ligament (ACLR) according to Pond and Nuki, verified by histological and magnetic resonance imaging (MRI) scoring as well as analysis of gene and protein expression.Materials and MethodsThe eight included skeletally mature female GM were assessed after ACLR in the left and a sham operation in the right knee, which served as control. 26 weeks after surgery the knee joints were scanned using a 3-Tesla high-field MR tomography unit with a 3 T CP Large Flex Coil. Standard proton-density weighted fat saturated sequences in coronal and sagittal direction with a slice thickness of 3 mm were used. The MRI scans were assessed by two radiologists according to a modified WORMS-score, the X-rays of the knee joints by two evaluators. Osteochondral plugs with a diameter of 4mm were taken for histological examination from either the main loading zone or the macroscopic most degenerated parts of the tibia plateau or condyle respectively. The histological sections were blinded and scored by three experts according to Little et al. Gene expression analysis was performed from surrounding cartilage. Expression of adamts4, adamts5, acan, col1A1, col2, il-1ß, mmp1, mmp3, mmp13, vegf was determined by qRT-PCR. Immunohistochemical staining (IH) of Col I and II was performed. IH was scored using a 4 point grading (0—no staining; 3-intense staining).Results and DiscussionSimilar signs of OA were evident both in ACLR and sham operated knee joints with the histological scoring result of the ACLR joints with 6.48 ± 5.67 points and the sham joints with 6.86 ± 5.84 points (p = 0.7953) The MRI scoring yielded 0.34 ± 0.89 points for the ACLR and 0.03 ± 0.17 for the sham knee joints. There was no correlation between the histological and MRI scores (r = 0.10021). The gene expression profiles as well as the immunohistochemical findings showed no significant differences between ACLR and sham knee joints. In conclusion, both knee joints showed histological signs of OA after 26 weeks irrespective of whether the ACL was resected or not. As MRI results did not match the histological findings, MRI was obviously unsuitable to diagnose the OA in GM. The analysis of the expression patterns of the 10 genes could not shed light on the question, whether sham operation also induced cartilage erosion or if the degeneration was spontaneous. The modified Pond-Nuki model may be used with reservation in the adult minipig to induce an isolated osteoarthritis.

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Identification of molecular markers for articular cartilage

Cited by 38 publications

References 32 publications

Identification of Fibroblast Growth Factor-18 as a Molecule to Protect Adult Articular Cartilage by Gene Expression Profiling

Identification of Fibroblast Growth Factor-18 as a Molecule to Protect Adult Articular Cartilage by Gene Expression Profiling

Metabolic enrichment of omega-3 polyunsaturated fatty acids does not reduce the onset of idiopathic knee osteoarthritis in mice

Osteoarthritis in the Knee Joints of Göttingen Minipigs after Resection of the Anterior Cruciate Ligament? Missing Correlation of MRI, Gene and Protein Expression with Histological Scoring

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