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1.
Paula Hoff Frank Buttgereit Gerd-Rüdiger Burmester Manuela Jakstadt Timo Gaber Kristin Andreas Georg Matziolis Carsten Perka Eric Röhner 《International orthopaedics》2013,37(1):145-151
Purpose
Two of the most common joint diseases are rheumatoid arthritis (RA) and osteoarthritis (OA). Cartilage degradation and erosions are important pathogenetic mechanisms in both joint diseases and have presently gained increasing interest. The aim of the present study was to investigate the effects of the synovial fluid environment of OA patients in comparison with synovial fluids of RA patients on human chondrocytes in vitro.Methods
Primary human chondrocytes were incubated in synovial fluids gained from patients with OA or RA. The detection of vital cell numbers was determined by histology and by using the Casy Cell Counter System. Cytokine and chemokine secretion was determined by a multiplex suspension array.Results
Microscopic analysis showed altered cell morphology and cell shrinkage following incubation with synovial fluid of RA patients. Detection of vital cells showed a highly significant decrease of vital chondrocyte when treated with RA synovial fluids in comparison with OA synovial fluids. An active secretion of cytokines such as vascular endothelial growth factor (VEGF) of chondrocytes treated with OA synovial fluids was observed.Conclusions
Significantly increased levels of various cytokines in synovial fluids of RA, and surprisingly of OA, patients were shown. Activation of pro-inflammatory cytokines of human chondrocytes by synovial fluids of OA patient supports a pro-inflammatory process in the pathogenesis of OA. 相似文献2.
Xiaozhou Ying Lei Peng Hua Chen Yue Shen Kehe Yu Shaowen Cheng 《International orthopaedics》2014,38(7):1519-1526
Purpose
Cordycepin, a nucleoside derivative isolated from Cordyceps, has been reported to exert anti-inflammatory, antitumor, antidiabetic and renoprotective effects. Osteoarthritis (OA) is a degenerative joint disease with an inflammatory component that drives the degradation of cartilage extracellular matrix. This study aimed to assess the effects of cordycepin on human OA chondrocytes.Methods
In this study, human OA chondrocytes were pretreated with cordycepin at 10, 50 or 100 μM and subsequently stimulated with interleukin-1β (IL-1β) (5 ng/ml) for 24 h. Production of prostaglandin E2 (PGE2) and nitric oxide (NO) were evaluated by the Griess reaction and an enzyme-linked immunosorbent assay (ELISA). Gene expression of matrix metalloproteinase (MMP)-13, IL-6, inducible nitric oxide synthase (iNOS) and cyclo-oxygenase (COX-2) was measured by real-time polymerase chain reaction (PCR). MMP-13 and IL-6 proteins in culture medium were determined using cytokine-specific ELISA. Western immunoblotting was used to analyse the iNOS and COX-2 protein production in culture medium. Nuclear factor kappa-B (NF-κB) activity regulation was explored using Western immunoblotting.Results
Pretreatment with cordycepin significantly inhibited the production of PGE2 and NO induced by IL-1β. Cordycepin also significantly decreased the IL-1β-stimulated gene expression and production of MMP-13, IL-6, iNOS and COX-2 in OA chondrocytes. Pretreatment with cordycepin attenuated IL-1β-induced activation of NF-κB by suppressing degradation of its inhibitory protein nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκB-α) in the cytoplasm.Conclusions
We show for the first time the anti-inflammatory activity of cordycepin in human OA chondrocytes. Thus, with this unique profile of actions, cordycepin may prove to be a potentially attractive and new therapeutic/preventive agent for OA. 相似文献3.
Jan Philipp Krüger Michaela Endres Katja Neumann Bruno Stuhlmüller Lars Morawietz Thomas H?upl Christian Kaps 《Journal of orthopaedic surgery and research》2012,7(1):1-10
Background
Microfracture is a first-line treatment option for cartilage repair. In microfracture, subchondral mesenchymal cortico-spongious progenitor cells (CSP) enter the defect and form cartilage repair tissue. The aim of our study was to investigate the effects of joint disease conditions on the in vitro chondrogenesis of human CSP.Methods
CSP were harvested from the subchondral bone marrow. CSP characterization was performed by analysis of cell surface antigen pattern and by assessing the chondrogenic, osteogenic and adipogenic differentiation potential, histologically. To assess the effect of synovial fluid (SF) on chondrogenesis of CSP, micro-masses were stimulated with SF from healthy (ND), osteoarthritis (OA) and rheumatoid arthritis donors (RA) without transforming growth factor beta 3.Results
CSP showed the typical cell surface antigen pattern known from mesenchymal stem cells and were capable of osteogenic, adipogenic and chondrogenic differentiation. In micro-masses stimulated with SF, histological staining as well as gene expression analysis of typical chondrogenic marker genes showed that SF from ND and OA induced the chondrogenic marker genes aggrecan, types II and IX collagen, cartilage oligomeric matrix protein (COMP) and link protein, compared to controls not treated with SF. In contrast, the supplementation with SF from RA donors decreased the expression of aggrecan, type II collagen, COMP and link protein, compared to CSP treated with SF from ND or OA.Conclusion
These results suggest that in RA, SF may impair cartilage repair by subchondral mesenchymal progenitor cells in microfracture, while in OA, SF may has no negative, but a delaying effect on the cartilage matrix formation. 相似文献4.
Yutaka Nakoshi Masahiro Hasegawa Koji Akeda Takahiro Iino Akihiro Sudo Toshimichi Yoshida Atsumasa Uchida 《Journal of orthopaedic science》2010,15(5):666-673
Background
Tenascin-C (TN-C) is expressed in the cartilage of osteoarthritis (OA). We examined whether TN-C was involved in cartilage repair of the diseased joints. Human articular cartilage samples were obtained from patients with OA and those with normal joints. 相似文献5.
6.
Bridgette D. Furman Collin L. Kent Janet L. Huebner Virginia B. Kraus Amy L. McNulty Farshid Guilak Steven A. Olson 《Journal of orthopaedic research》2018,36(4):1220-1227
7.
Natthaphon Saetan Sittisak Honsawek Aree Tanavalee Pongsak Yuktanandana Surapoj Meknavin Srihatach Ngarmukos Thanathep Tanpowpong Vinai Parkpian 《International orthopaedics》2014,38(5):1099-1104
Purpose
Recent evidence suggests that angiogenesis and inflammation contribute to the development and progression of osteoarthritis (OA). The purpose of this study was to investigate vascular endothelial growth factor (VEGF) levels in plasma and synovial fluid of patients with knee OA and to determine the relationship of VEGF levels with disease severity in knee OA.Methods
A total of 100 subjects were enrolled in this study (80 knee OA patients and 20 healthy controls). Plasma and synovial fluid VEGF levels were analysed using enzyme-linked immunosorbent assay. VEGF expressions in synovial membrane and articular cartilage samples were assessed using immunohistochemistry.Results
VEGF level in synovial fluid of knee OA patients was tenfold higher than that in paired plasma (P < 0.001). Both plasma and synovial fluid VEGF exhibited a positive correlation with radiographic severity (r = 0.454 and r = 0.727, P < 0.001, respectively). VEGF expression was highly detectable in synovial lining cells and articular chondrocytes of knee OA patients.Conclusions
VEGF levels in both plasma and synovial fluid were positively correlated with the severity of knee OA. Therefore, VEGF may be useful for monitoring OA severity and could play a substantial role in the development and progression of knee OA. 相似文献8.
Background and purpose
Little is known about biochemical mediators that correlate with the initiation and progression of knee osteoarthritis (OA). We therefore valuated the roles of cytokines and metalloenzymes in knee OA in relation to OA grading, age, and BMI.Patients and methods
A multiplex ELISA-based immunoassay (Luminex technology) was used to measure biochemical mediators in the synovial fluid (SF) of 82 patients undergoing knee surgery. All patients were classified according to age, BMI, and OA grade. 24 patients had no signs of OA (knee reconstruction surgeries). The mediators that were tested for included interleukins (IL-1Ra, IL-6, IL-7, and IL-18), chemokines (CCL2 (MCP-1), CCL3 (MIP-1a), and CXCL8 (IL-8)), growth factors (HGF and VEGF), and matrix metalloproteinases (MMP-1, MMP-2, MMP-9, and MMP-13).Results
There was a correlation between IL-7 levels in SF and age (p < 0.01). The 11 highest IL-7 levels were seen in patients who were aged between 59 and 72 but had different OA grades. In contrast, all patients who had severe OA in all 3 knee compartments (pan-OA) had only low or medium IL-7 levels. There was a negative correlation between MMP-1 levels in synovial fluid and grade of OA (p < 0.001). Correlation studies between pairs of mediators revealed two groups of mediators that are important in OA progression, dominated by MCP-1 and IL-1Ra.Interpretation
IL-7 levels in SF are elevated in elderly people suffering from OA of different grades, but they are depressed in patients with severe 3-compartment OA, possibly due to widely impaired chondrocytes embedded in the affected cartilage tissue. The observed decrease in MMP-1 levels in SF, which is dependent on the severity of OA, may be caused by deterioration of superficial cartilage layers during progression of OA.List of abbreviations
- BMI
- body mass index
- CCL
- chemokine (C-C motif) ligand
- CXCL
- chemokine (C-X-C motif) ligand
- HGF
- hepatocyte growth factor
- ICRS
- International Cartilage Repair Society
- IL
- interleukin
- IL-1Ra
- IL-1 receptor antagonist
- MCP
- monocyte chemoattractant protein
- MIP
- macrophage inflammatory protein
- MMP
- matrix metalloproteinase
- OA
- osteoarthritis
- SF
- synovial fluid
- VEGF
- vascular endothelial growth factor
9.
Kan Yoshida Shigeyuki Takatsuka Eriko Hatada Hiroyuki Nakamura Akira Tanaka Koichiro Ueki Kiyomasa Nakagawa Yasunori Okada Etsuhide Yamamoto Ryuuzi Fukuda 《Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics》2006,102(1):22-27
OBJECTIVE: To investigate whether matrix metalloproteinases (MMPs) and/or aggrecanase in synovial fluid can be used as biochemical markers in the diagnosis of internal derangement (ID) of the temporomandibular joint (TMJ). STUDY DESIGN: Forty-four samples of synovial fluid were obtained from 35 patients with ID and osteoarthritis (OA) and 15 normal samples from 10 asymptomatic volunteers. MMP-2, -9, and aggrecanase in the synovial fluid were examined by immunoblotting. RESULTS: The incidences of MMP-2, -9, and aggrecanase expression in the ID and OA group were significantly higher than those in the normal group (P < .05). Those with anterior disc displacement without reduction and severe OA showed significantly high expression of MMP-9 compared with other disease subgroups (P < .05). Conversely, comparatively high expression of MMP-2 and aggrecanase was shown in the early-stage OA group. However, there was no significant difference in expression of MMP-2 and aggrecanase among disease subgroups. CONCLUSIONS: These findings suggested that expression of aggrecanase could be a potential biochemical marker for articular cartilage degradation in ID of the TMJ. 相似文献
10.
Michaela Endres Katja Neumann Bei Zhou Undine Freymann David Pretzel Marcus Stoffel Raimund W Kinne Christian Kaps 《Journal of orthopaedic surgery and research》2012,7(1):1-14
Background
Scaffold-assisted autologous chondrocyte implantation is an effective clinical procedure for cartilage repair. From the regulatory point of view, the ovine model is one of the suggested large animal models for pre-clinical studies. The aim of our study was to evaluate the in vitro re-differentiation capacity of expanded ovine chondrocytes in biomechanically characterized polyglycolic acid (PGA)/fibrin biomaterials for scaffold-assisted cartilage repair.Methods
Ovine chondrocytes harvested from adult articular cartilage were expanded in monolayer and re-assembled three-dimensionally in PGA-fibrin scaffolds. De- and re-differentiation of ovine chondrocytes in PGA-fibrin scaffolds was assessed by histological and immuno-histochemical staining as well as by real-time gene expression analysis of typical cartilage marker molecules and the matrix-remodelling enzymes matrix metalloproteinases (MMP) -1, -2 and ?13 as well as their inhibitors. PGA scaffolds characteristics including degradation and stiffness were analysed by electron microscopy and biomechanical testing.Results
Histological, immuno-histochemical and gene expression analysis showed that dedifferentiated chondrocytes re-differentiate in PGA-fibrin scaffolds and form a cartilaginous matrix. Re-differentiation was accompanied by the induction of type II collagen and aggrecan, while MMP expression decreased in prolonged tissue culture. Electron microscopy and biomechanical tests revealed that the non-woven PGA scaffold shows a textile structure with high tensile strength of 3.6 N/mm2 and a stiffness of up to 0.44 N/mm2, when combined with gel-like fibrin.Conclusion
These data suggest that PGA-fibrin is suited as a mechanically stable support structure for scaffold-assisted chondrocyte grafts, initiating chondrogenic re-differentiation of expanded chondrocytes. 相似文献11.
12.
Altered in vitro chondrogenic properties of chondrocytes harvested from unaffected cartilage in osteoarthritic joints 总被引:1,自引:0,他引:1
Yang KG Saris DB Geuze RE van Rijen MH van der Helm YJ Verbout AJ Creemers LB Dhert WJ 《Osteoarthritis and cartilage / OARS, Osteoarthritis Research Society》2006,14(6):561-570
13.
Chengjie Xiong MD PhD Bo Huang MD PhD Yanping Cun MD PhD Bayan G. Aghdasi MD Yue Zhou MD PhD 《Clinical orthopaedics and related research》2014,472(6):1943-1954
Background
Type 1 Modic changes are characterized by edema, vascularization, and inflammation, which lead to intervertebral disc degeneration. Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine closely related to the inflammatory cytokines detected in degenerative intervertebral disc tissues. However, the existence and role of MIF and its receptor CD74 in intervertebral disc degeneration have not been elucidated.Questions/purposes
We asked whether (1) MIF and its receptor CD74 are expressed in cartilage end plates with Type 1 Modic changes, (2) MIF is associated with cartilage end plate degeneration, (3) the MIF antagonist (S, R)-3(4-hydroxyphenyl)-4, 5-dihydro-5-isoxazole acetic acid methyl ester (ISO-1) suppresses MIF-induced inflammatory cytokine release, and (4) inflammatory cytokines are released by cartilage end plate chondrocytes via CD74 by activating the CD74 antibody (CD74Ab).Methods
We examined MIF and CD74 expression by human cartilage end plate chondrocytes and tissues with Type 1 Modic changes from eight patients using immunocytofluorescence and immunohistochemistry. MIF production by the chondrocytes was assessed by ELISA and PCR. We compared cytokine release by chondrocytes treated with MIF in the presence or absence of exogenous ISO-1 by ELISA. Cytokine release by chondrocytes after treatment with CD74Ab was determined by ELISA.Results
MIF was expressed in degenerated human cartilage end plate tissues and chondrocytes. Lipopolysaccharide and tumor necrosis factor α (TNF-α) upregulated MIF expression and increased MIF secretion in chondrocytes in a dose-dependent manner. MIF increased the secretion of IL-6, IL-8, and prostaglandin E2 (PGE2) in a dose-dependent manner. ISO-1 reduced the secretion of IL-6, IL-8, and PGE2. CD74Ab activated CD74 and induced release of inflammatory cytokines.Conclusions
Chondrocytes in cartilage end plate with Type 1 Modic changes express MIF and its receptor CD74. MIF might promote the inflammatory response through CD74. MIF-induced cytokine release appears to be suppressed by ISO-1, and CD74Ab could induce cytokine release.Clinical Relevance
The MIF/CD74 pathway may represent a crucial target for treating disc degeneration since inhibiting the function of MIF with its antagonist ISO-1 can reduce MIF-induced inflammation and exert potent therapeutic effects. 相似文献14.
Struglics A Larsson S Pratta MA Kumar S Lark MW Lohmander LS 《Osteoarthritis and cartilage / OARS, Osteoarthritis Research Society》2006,14(2):101-113
OBJECTIVE: To identify the major aggrecanase- and matrix metalloproteinase (MMP)-generated aggrecan fragments in human osteoarthritis (OA) synovial fluid and in human OA joint cartilage. METHOD: Aggrecan fragments were prepared by CsCl gradient centrifugation. Fragment distributions were compared with aggrecanase-1 (ADAMTS-4) and MMP-3 digested human aggrecan by analysis with neoepitope antibodies and an anti-G1 domain antibody, using Western immuno-blots. RESULTS: The overall fragment pattern of OA synovial fluid aggrecan was similar to the fragment pattern of cartilage aggrecan cleaved in vitro by ADAMTS-4. However, multiple glycosaminoglycan (GAG) containing aggrecanase and MMP-generated aggrecan fragments were identified in OA synovial fluid and some of these fragments were produced by the action of both types of proteinases. The synovial fluid content of large size aggrecan fragments with (374)ARGS- and (342)FFGV- N-terminals was about 107 and 40 pmoles per ml, respectively, out of a total concentration of aggrecan fragments of about 185 pmoles per ml. OA synovial fluid contained insignificant amounts of the G1-IPEN(341) fragment as compared to the G1-TEGE(373) fragment, while OA cartilage contained significant amounts of both fragments. OA cartilage contained several GAG-containing aggrecan fragments with N-terminals of G1- or (342)FFGV- but no fragments with an N-terminal of (374)ARGS-. CONCLUSIONS: The overall pattern of aggrecan fragments in human OA synovial fluid and cartilage supports an important role for aggrecanase in aggrecan degradation. However, the fragment patterns and their differential distribution between cartilage and synovial fluid are consistent with the existence of at least two proteolytic pathways for aggrecan degradation in human OA, generating both (342)FFGV- and (374)ARGS-fragments. 相似文献
15.
Nathan P. Thomas Wesley J. Wu Braden C. Fleming Fangyuan Wei Qian Chen Lei Wei 《BMC musculoskeletal disorders》2017,18(1):556
Background
The objective of this study was to evaluate the extent of stromal cell-derived factor-1’s (SDF-1) involvement in the pathogenesis of idiopathic versus post-traumatic OA by comparing differences in synovial membrane morphology, SDF-1 synovial fluid (SF) concentrations, and matrix metalloproteinase-13 (MMP-13) SF concentrations.Methods
Thirty-six 3-month-old Hartley guinea pigs were obtained and divided into 6 groups. Upon sacrifice, India Ink staining was used to evaluate gross morphology, Safranin O/Fast green staining was used to assess cartilage damage, H/E staining was employed to visualize the synovium, and SF samples were obtained for biochemical analyses. Sandwich ELISA was used to quantify the SF concentrations of SDF-1 and MMP-13.Results
12 month-old, idiopathic OA guinea pigs and 5.5 month-old ACLT animals had comparable cartilage damage when evaluated by the Modified Mankin Score. SDF-1 and MMP-13 concentrations were not statistically different between the two groups. The synovial membrane of the 5.5 month ACLT group had severe synovitis compared to the idiopathic OA group.Conclusion
In this study, it was found that synovial inflammation, independent of cartilage morphology, SDF-1 concentration, and MMP-13 concentration, was markedly different between idiopathic and post-traumatic OA. These results highlight the differing morphological and biochemical profiles of post-traumatic versus idiopathic osteoarthritis and calls for a more thorough examination of the sole of the synovial membrane in the pathogenesis of post-traumatic osteoarthritis.16.
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19.
H. Tohyama K. Yasuda A. Minami T. Majima N. Iwasaki T. Muneta I. Sekiya K. Yagishita S. Takahashi K. Kurokouchi Y. Uchio J. Iwasa M. Deie N. Adachi K. Sugawara M. Ochi 《Journal of orthopaedic science》2009,14(5):579-588
Background
New tissue-engineering technology was developed to create a cartilage-like tissue in a three-dimensional culture using atelocollagen gel. The minimum 2-year followup outcome of transplanting autologous chondrocytes cultured in atelocollagen gel for the treatment of full-thickness defects of cartilage in knees was reported from the single institution. The present multicenter study was conducted to determine clinical and arthroscopic outcomes in patients who underwent atelocollagen-associated autologous chondrocyte implantation for the repair of chondral defects of the knees.Methods
At six medical institutes in Japan, we prospectively evaluated the clinical and arthroscopic outcomes of transplanting autologous chondrocytes cultured in atelocollagen gel for the treatment of full-thickness defects of cartilage in 27 patients (27 knees) with cartilage lesions on a femoral condyle or on a patellar facet over 24 months.Results
The Lysholm score significantly increased from 60.0 ± 13.7 points to 89.8 ± 9.5 points (P = 0.001). Concerning the ICRS grade for arthroscopic appearance, 6 knees (24%) were assessed as grade I (normal) and 17 knees (68%) as grade II (nearly normal). There were few adverse features, except for detachment of the graft in two cases.Conclusions
We concluded that transplanting chondrocytes in a newly formed matrix of atelocollagen gel can promote restoration of the articular cartilage of the knee. 相似文献20.
Wendan Cheng Dongying Wu Qiang Zuo Zhen Wang Weimin Fan 《International orthopaedics》2013,37(10):2065-2070