scholarly journals The utility of measuring C-terminal telopeptides of collagen type II (CTX-II) in serum and synovial fluid samples for estimation of articular cartilage status in experimental models of destructive joint diseases

2006 ◽  
Vol 14 (7) ◽  
pp. 670-679 ◽  
Author(s):  
S. Oestergaard ◽  
L. Chouinard ◽  
N. Doyle ◽  
M.A. Karsdal ◽  
S.Y. Smith ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Synovial Fluid ◽  
Collagen Type ◽  
Experimental Models ◽  
Joint Diseases ◽  
Type Ii ◽  
Collagen Type Ii

Phenotypic maintenance of articular chondrocytes in vitro requires BMP activity

2007 ◽  
Vol 20 (03) ◽  
pp. 185-191 ◽  
Author(s):  
A. O. Oshin ◽  
E. Caporali ◽  
C. R. Byron ◽  
A. A. Stewart ◽  
M. C. Stewart
Keyword(s):  
Articular Cartilage ◽  
Collagen Type ◽  
Articular Chondrocytes ◽  
Soluble Form ◽  
Mrna Levels ◽  
Type Ii ◽  
Collagen Type Ii ◽  
Endogenous Expression ◽  
Chondrocytic Phenotype

SummaryArticular chondrocytes are phenotypically unique cells that are responsible for the maintenance of articular cartilage. The articular chondrocytic phenotype is influenced by a range of soluble factors. In particular, members of the bone morphogenetic protein (BMP) family support the articular chondrocytic phenotype and stimulate synthesis of cartilaginous matrix. This study was carried out to determine the importance of BMPs in supporting the differentiated phenotype of articular chondrocytes in vitro. Exogenous BMP-2 supported expression of collagen type II and aggrecan in monolayer chondrocyte cultures, slowing the dedifferentiation process that occurs under these conditions. In contrast, BMP-2 had little effect on expression of these genes in three-dimensional aggregate cultures. Endogenous BMP-2 expression was lost in monolayer cultures, coincident with the down-regulation of collagen type II and aggrecan mRNAs, whereas BMP-2 mRNA levels were stable in aggregate cultures. Antagonism of endogenous BMP activity in aggregate cultures by Noggin or a soluble form of the BMP receptor resulted in reduced expression of collagen type II and aggrecan mRNAs, reduced collagen type II protein and sulfated glycosaminoglycan (GAG) deposition into the aggregate matrices and reduced secretion of GAGs into the culture media. These results indicate that endogenous BMPs are required for maintenance of the differentiated articular chondrocytic phenotype in vitro. These findings are of importance to cell-based strategies designed to repair articular cartilage. Articular chondrocytes require conditions that will support endogenous expression of BMPs to maintain the specialized phenotype of these cells.

Enhanced Early Tissue Regeneration after Matrix-Assisted Autologous Mesenchymal Stem Cell Transplantation in Full Thickness Chondral Defects in a Minipig Model

2009 ◽  
Vol 18 (8) ◽  
pp. 923-932 ◽  
Author(s):  
Martin Jung ◽  
Balazs Kaszap ◽  
Anna Redöhl ◽  
Eric Steck ◽  
Steffen Breusch ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Collagen Type ◽  
Type I ◽  
Type Ii ◽  
Collagen Type Ii ◽  
Histomorphometric Analysis ◽  
Tissue Quality ◽  
Repair Tissue ◽  
Adult Mesenchymal Stem Cells ◽  
Defect Area

Adult mesenchymal stem cells (MSCs) are an attractive cell source for new treatment strategies in regenerative medicine. This study investigated the potential effect of matrix assisted MSC transplantation for articular cartilage regeneration in a large-animal model 8 weeks postoperatively. MSCs from bone marrow aspirates of eight Goettingen minipigs were isolated and expanded prior to surgery. Articular cartilage defects of 5.4 mm were created bilaterally in the medial patellar groove without penetrating the subchondral bone plate. Defects were either left empty ( n = 4), covered with a collagen type I/III membrane ( n = 6) or additionally treated with autologous MSC transplantation (2 × 106; n = 6). After 8 weeks animals were euthanized and the defect area was assessed for its gross appearance. Histomorphological analysis of the repair tissue included semiquantitative scoring (O'Driscoll score) and quantitative histomorphometric analysis for its glycosaminoglycan (GAG) and collagen type II content. All membranes were found to cover the defect area 8 weeks postoperatively. Median defect filling was 115.8% (membrane), 117.8% (empty), and 100.4% (MSC), respectively (not significant). Histomorphological scoring revealed significantly higher values in MSC-treated defects (median 16.5) when compared to membrane treatment (median 9.5) or empty defects (median 11.5; p = 0.015 and p = 0.038). Histomorphometric analysis showed larger GAG/collagen type II-positive areas in the MSC-treated group (median 24.6%/29.5% of regeneration tissue) compared to 13.6%/33.1% (empty defects) and 1.7%/6.2% (membrane group; p = 0.066). Cell distribution was more homogeneous in MSC compared to membrane-only group, where cells were found mainly near the subchondral zone. In conclusion, autologous matrix-assisted MSC transplantation significantly increased the histomorphological repair tissue quality during early articular cartilage defect repair and resulted in higher GAG/collagen type II-positive cross-sectional areas of the regenerated tissue.

Inducible chondrocyte-specific overexpression of BMP2 in young mice results in severe aggravation of osteophyte formation in experimental OA without altering cartilage damage

2014 ◽  
Vol 74 (6) ◽  
pp. 1257-1264 ◽  
Author(s):  
E N Blaney Davidson ◽  
E L Vitters ◽  
M B Bennink ◽  
P L E M van Lent ◽  
A P M van Caam ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Structural Damage ◽  
Medial Meniscus ◽  
Collagen Type ◽  
Cartilage Damage ◽  
Bone Morphogenetic Protein 2 ◽  
Type Ii ◽  
Collagen Type Ii ◽  
Osteophyte Formation ◽  
Young Mice

ObjectivesIn osteoarthritis (OA) chondrocytes surrounding lesions express elevated bone morphogenetic protein 2 (BMP2) levels. To investigate the functional consequence of chondrocyte-specific BMP2 expression, we made a collagen type II dependent, doxycycline (dox)-inducible BMP2 transgenic mouse and studied the effect of elevated BMP2 expression on healthy joints and joints with experimental OA.MethodsWe cloned a lentivirus with BMP2 controlled by a tet-responsive element and transfected embryos of mice containing a collagen type II driven cre-recombinase and floxed rtTA to gain a mouse expressing BMP2 solely in chondrocytes and only upon dox exposure (Col2-rtTA-TRE-BMP2). Mice were treated with dox to induce elevated BMP2 expression. In addition, experimental OA was induced (destabilisation of the medial meniscus model) with or without dox supplementation and knee joints were isolated for histology.ResultsDox treatment resulted in chondrocyte-specific upregulation of BMP2 and severely aggravated formation of osteophytes in experimental OA but not in control mice. Moreover, elevated BMP2 levels did not result in alterations in articular cartilage of young healthy mice, although BMP2-exposure did increase VDIPEN expression in the articular cartilage. Strikingly, despite apparent changes in knee joint morphology due to formation of large osteophytes there were no detectible differences in articular cartilage: none with regard to structural damage nor in Safranin O staining intensity when comparing destabilisation of the medial meniscus with or without dox exposure.ConclusionsOur data show that chondrocyte-specific elevation of BMP2 levels does not alter the course of cartilage damage in an OA model in young mice but results in severe aggravation of osteophyte formation.

Sign in / Sign up

Export Citation Format

Share Document