The apparent connection of galectin-3 to chondrocyte survival and osteoarthritis-like cartilage modifications in animal models provided incentive for the mapping of seven members of this family of adhesion/growth-regulatory proteins in human cartilage specimens. Starting with work in vitro, RT-qPCR analyses and immunocytochemistry revealed gene transcription and protein presence in cultured OA chondrocytes, especially for galectin-1, galectin-3 and galectin-8. Immunohistochemistry in clinical specimens with mild and severe cartilage degeneration detected galectins in chondrocytes-with upregulation, especially of galectin-1 in areas of severe degeneration-accompanied by α2,6-sialylation in the pericellular matrix. Given the possibility for additive/antagonistic activities between galectins, these results direct further research toward examining cellular effects of (1) these proteins (alone or in combination) on chondrocytes and (2) remodeling of the chondrocyte glycophenotype.

IntroductionThis study aimed to characterize the glycophenotype of osteoarthritic cartilage and human chondrocytes.MethodsArticular knee cartilage was obtained from nine osteoarthritis (OA) patients. mRNA levels for 27 glycosyltransferases were analyzed in OA chondrocytes using RT-qPCR. Additionally, N- and O-glycans were quantified using mass-spectrometry. Histologically, two cartilage areas with Mankin scores (MS) either ≤4 or ≥9 were selected from each patient representing areas of mild and severe OA, respectively. Tissue sections were stained with (1) a selected panel of plant lectins for probing into the OA glycophenotype, (2) the human lectins galectins-1 and -3, and (3) the glycoprotein asialofetuin (ASF) for visualizing β-galactoside-specific endogenous lectins.ResultsWe found that OA chondrocytes expressed oligomannosidic structures as well as non-, mono- and disialylated complex-type N-glycans, and core 2 O-glycans. Reflecting B4GALNT3 mRNA presence in OA chondrocytes, LacdiNAc-terminated structures were detected. Staining profiles for plant and human lectins were dependent on the grade of cartilage degeneration, and ASF-positive cells were observed in significantly higher rates in areas of severe degeneration.ConclusionsIn summary, distinct aspects of the glycome in OA cartilage are altered with progressing degeneration. In particular, the alterations measured by galectin-3 and the pan-galectin sensor ASF encourage detailed studies of galectin functionality in OA.

chondro-induction). Chondro-induction was lower (1.3AE0.4) and less reproducible when coculture was performed with M14 and did not occur with skin fibroblasts. GAG contents of constructs generated by solely macrophages were undetectable. Histological analyses of constructs confirmed the biochemical results. In the coculture there was no modulation of the chondrogenic genes. As compared to monocultures, in co-culture MSC and M24 numbers decreased less markedly (at day 7, MSC were 84% and 42% of the initial number, M24 were 26% of the initial number and undetectable, respectively for co-cultured and monocultured cells). Conclusions: We have demonstrated that coculture MSC/M42 results in synergistic cartilage tissue formation, which is not mediated by soluble factors alone. Further studies are envisioned to investigate whether M42 modulate the survival of specific MSC sub-populations. Finally, in vivo studies are necessary to assess the clinical relevance of our findings in the context of cartilage repair.

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Rheumatoid arthritis (RA) synoviocytes present an increased mitochondrial genome mutagenesis, leading to mitochondrial alterations that might be participating in the pathogenesis of the disease. This study was performed to examine whether mitochondrial dysfunction is involved in joint destruction and inflammation in RA in relation to the expression of matrix metalloproteinases-1 and-3 (MMP-1 and MMP-3) and vascular endothelial growth factor (VEGF) in normal human synoviocytes. Methods: Normal human synoviocytes were treated with the commonly used mitochondrial respiratory inhibitor oligomycin (OLI) (10 mg/ml) for 24