Objective: To identify the molecular differences between the transient and permanent chondrocyte phenotype in osteophytic and articular cartilage. Methods: Total RNA was isolated from the cartilaginous layer of osteophytes and from intact articular cartilage from knee joints of 15 adult human donors and subjected to cDNA microarray analysis. The differential expression of relevant genes between these two cartilaginous tissues was additionally validated by quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and by immunohistochemistry. Results: Among 47,000 screened transcripts, 600 transcripts were differentially expressed between osteophytic and articular chondrocytes. Osteophytic chondrocytes were characterized by increased expression of genes involved in the endochondral ossification process [bone gamma-carboxyglutamate protein/osteocalcin (BGLAP), bone morphogenetic protein-8B (BMP8B), collagen type I, alpha 2 (COL1A2), sclerostin (SOST), growth arrest and DNA damage-induced gene 45ß (GADD45ß), runt-related transcription factor 2 (RUNX2)], and genes encoding tissue remodeling enzymes [matrix metallopeptidase (MMP)9, 13, hyaluronan synthase 1 (HAS1)]. Articular chondrocytes expressed increased transcript levels of antagonists and inhibitors of the BMP-and Wnt-signaling pathways [Gremlin-1 (GREM1), frizzled-related protein (FRZB), WNT1 inducible signaling pathway protein-3 (WISP3)], as well as factors that inhibit terminal chondrocyte differentiation and endochondral bone formation [parathyroid hormone-like hormone (PTHLH), sex-determining region Y-box 9 (SOX9), stanniocalcin-2 (STC2), S100 calcium binding protein A1 (S100A1), S100 calcium binding protein B (S100B)]. Immunohistochemistry of tissue sections for GREM1 and BGLAP, the two most prominent differentially expressed genes, confirmed selective detection of GREM1 in articular chondrocytes and that of BGLAP in osteophytic chondrocytes and bone. Conclusions: Osteophytic and articular chondrocytes significantly differ in their gene expression pattern. In articular cartilage, a prominent expression of antagonists inhibiting the BMP-and Wnt-pathway may serve to lock and stabilize the permanent chondrocyte phenotype and thus prevent their terminal differentiation. In contrast, osteophytic chondrocytes express genes with roles in the endochondral ossification process, which may account for their transient phenotype.
Articular cartilage is an avascular, bradytrophic tissue in which the chondrocytes physiologically maintain their unique differentiation status throughout life. In contrast to chondrocytes of the fetal growth plate, articular chondrocytes are postmitotic cells that do not undergo terminal differentiation, and their extracellular matrix does not calcify above the tidemark. Bone marrow-stimulating techniques, such as microfracturing of the subchondral bone plate, are simple, minimally invasive, and cost-effective cartilage repair approaches that are frequently applied in clinical settings. Unfortunately, the ingrowing osteochondral progenitor cells often fail to undergo complete chondrogenic differentiation, which leads to the formation of inferior fibrocar-
The aim of this study was to investigate the effect of transplanted chondrocytes on endochondral bone formation in cartilage repair tissue. In the knee joint of miniature pigs, cartilage lesions were treated by microfracturing and were then either left empty, covered with a collagen membrane, or treated by matrix-associated autologous chondrocyte transplantation. In control lesions, the subchondral bone plate was left intact (partial-thickness lesion). The repair tissues were analyzed after 12 weeks by histological methods focusing on bone formation and vascularization. The effect of chondrocytes on angiogenesis was assessed by in vitro assays. The presence of antiangiogenic proteins in cartilage repair tissue, including thrombospondin-1 (TSP-1) and chondromodulin-I (ChM-I), was detected immunohistochemically and their expression in chondrocytes and bone marrow stromal cells was measured by quantitative RT-PCR. Significant outgrowths of subchondral bone and excessive endochondral ossification within the repair tissue were regularly observed in lesions with an exposed or microfractured subchondral bone plate. In contrast, such excessive bone formation was significantly inhibited by the additional transplantation of chondrocytes. Cartilaginous repair tissue that resisted ossification was strongly positive for the antiangiogenic proteins, TSP-1 and ChM-I, which were, however, not detectable in vascularized osseous outgrowths. Chondrocytes were identified to be the major source of TSP-1- and ChM-I expression and were shown to counteract the angiogenic activity of endothelial cells. These data suggest that the resistance of cartilaginous repair tissue against endochondral ossification following the transplantation of chondrocytes is associated with the presence of antiangiogenic proteins whose individual relevance has yet to be further explored.
The CLS((R)) Spotorno stem allows excellent long-term results in cementless hip arthroplasty, leaving only minimal options for substantial improvements. Our findings on progressive stress shielding point towards a more diaphyseal load transfer of the CLS stem.
Either an extensor indicis transposition (EIT) or an intercalated free tendon graft (FTG) can be used for secondary reconstruction of the extensor pollicis longus (EPL) tendon. We reviewed 1469 cases of extensor tendons repaired between 1992 and 2003 and compared the results. In only 55 patients was an isolated secondary reconstruction of the EPL done. Forty-five patients (82%) were available for clinical follow-up after a mean of 4.3 (range 2-11) years (28 (62%) who had EIT and 17 (38%) who had FTG). Thumb function was assessed postoperatively using Geldmacher's criteria, and the uninjured thumb served as control. The comparison showed no significant differences between the procedures for the single variables evaluated, or for the injured and other (uninjured) thumb in either group. For isolated secondary reconstruction of the EPL tendon, both the extensor indicis transposition and a free autologous tendon graft successfully restore thumb function. Therefore, both surgical techniques can be considered equal alternatives.
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