Sirtuin 1 enzymatic activity is required for cartilage homeostasis in vivo in a mouse model.

in Arthritis and Rheumatism (2013), 65(1), 159-66

OBJECTIVE: We and others previously demonstrated that sirtuin 1 (SIRT-1) regulates apoptosis and cartilage-specific gene expression in human chondrocytes and mouse models. This study was undertaken to ... [more ▼]

OBJECTIVE: We and others previously demonstrated that sirtuin 1 (SIRT-1) regulates apoptosis and cartilage-specific gene expression in human chondrocytes and mouse models. This study was undertaken to determine if SIRT-1 enzymatic activity plays a protective role in cartilage homeostasis in vivo, by investigating mice with SIRT-1 mutations to characterize their cartilage. METHODS: Articular cartilage was harvested from the paws and knees of 5- and 6-month-old wild-type (WT) mice and mice homozygous for SIRT-1(tm2.1Mcby) (SIRT-1(y/y) ), an allele carrying a point mutation that encodes a SIRT-1 protein with no enzymatic activity (y/y mice). Mice ages 2 days old and 6-7 days old were also examined. Mouse joint cartilage was processed for histologic examination or biochemical analyses of chondrocyte cultures. RESULTS: We found that articular cartilage tissue sections from y/y mice of up to 6 months of age contained reduced levels of type II collagen, aggrecan, and glycosaminoglycan compared to sections from WT mice. In contrast, protein levels of matrix metalloproteinase 8 (MMP-8), MMP-9, and MMP-13 were elevated in the cartilage of y/y mice. In addition, chondrocyte apoptosis was elevated in SIRT-1 mutant mice as compared to their WT littermates. Consistent with these observations, protein tyrosine phosphatase 1b was elevated in the y/y mice. CONCLUSION: Our in vivo findings in this animal model demonstrate that mice with defective SIRT-1 also have defective cartilage, with elevated rates of cartilage degradation with age. Hence, normal cartilage homeostasis requires enzymatically active SIRT-1 protein. [less ▲]

Association entre l'hypertrophie du chondrocyte et l'angiogenèse du cartilage dans l'arthrose

Conference (2012, December)

Association between chondrocytes hypertrophy and angiogenesis of cartilage in osteoarthritis

Poster (2012, November 13)

Alginate-chitosan hydrogel beads decrease inflammatory and anabolic mediators produced by human chondrocytes

Poster (2012, September 17)

Introduction Osteoarthritis (OA) is the most prevalent arthritic disease. It is characterized by the degradation of articular cartilage accompanied by the inflammation of the synovial membrane and ... [more ▼]

Introduction Osteoarthritis (OA) is the most prevalent arthritic disease. It is characterized by the degradation of articular cartilage accompanied by the inflammation of the synovial membrane and sclerosis of subchondral bone. OA produces pain and loss of joint function. Today, there is no treatment to cure OA or to delay effectively its progression. Current treatments are mainly based on alleviation of painful symptoms but are unable to restore the cartilage. The development of new scaffold for tissue engineering is a promising approach. Herein, we report the effects of alginate-chitosan hydrogel (AC) beads on the metabolism of chondrocytes. Materials and Methods Human chondrocytes were isolated from OA cartilage and cultured either in AC beads or in alginate (A) beads. AC beads were prepared using chitosan (KiOmedine-CsU ultra-pure chitosan from KitoZyme, Herstal, Belgium) and alginate. The two polymer solutions were prepared separately before being mixed together. Cells were added to the polymer mixture and the cell-containing beads prepared by precipitation in a calcium chloride solution. The chondrocytes embedded in the beads were then cultured in a well defined culture medium for up to 28 days. Cell viability was determined by quantifying the release of lactate deshydrogenase (LDH) in the culture supernatant. Interleukin (IL)-6 and -8, prostaglandin E2 (PGE2), matrix metalloprotease (MMP)-3 and aggrecan were measured by specific ELISA. Finally, nitric oxide (NO) was measured by the Griess reaction. Results Histological analysis of AC beads showed chondrocytes in contact with chitosan trabeculae that were homogeneously distributed in the alginate matrix. LDH level remained below the limit of detection over the culture duration suggesting that AC had no cytotoxic effect. By comparison with culture in A beads, chondrocytes in AC beads produced significantly higher amounts of aggrecan but lowered the levels of MMP-3, NO, IL-6, IL-8 and PGE2. Discussion The contact between cells and AC beads components led us to hypothesize that chitosan has beneficial effects such as anti-inflammatory, anti-catabolic and stimulating effects on cartilage matrix components. Conclusion These particular effects indicate that AC beads are potentially new carriers for cell transplantation, particularly to repair cartilage defects. They could be further developed under various formulations, such as microbeads in combination with hydrogel for efficient viscossuplementation. [less ▲]

New alginate-chitosan hydrogel to repair cartilage. A partner ship between www.bcru.be and www.kitozyme.com

Poster (2012, April 19)

Bone sialoprotein: a key mediator of the angiogenic activity of hypertrophic osteoarthritic chondrocytes

Poster (2012, April)

Association entre l'hypertrophie du chondrocyte et l'angiogenèse du cartilage dans l'arthrose

in Revue du Rhumatisme (2012), 79(S), 105-106

La bone sialoproteine: un facteur clé dans la pathogénie de l'arthrose

in Revue du Rhumatisme (2012), 79(S), 106

Epigenetics, sirtuins and osteoarthritis.

in Joint, bone, spine : revue du rhumatisme (2012), 79(6), 570-3

Epigenetics, modifications of the DNA other than changes on the DNA sequences, is frequently studied in cancer research and aging. DNA methylation, mi-RNA, and histones deacetylation are investigated in ... [more ▼]

Epigenetics, modifications of the DNA other than changes on the DNA sequences, is frequently studied in cancer research and aging. DNA methylation, mi-RNA, and histones deacetylation are investigated in different pathologies, including inflammatory diseases and age-related diseases such as osteoarthritis (OA). In this review, we focus on the chromatin-modifying enzymes in arthritic pathologies, and more particularly on Sirtuins. We also review the role of Sirt1 in OA, which has been highlighted in recent publications, and examine the possible protective role Sirt1 could play in this disease. Moreover, we discuss the possible therapeutic target of such a protein, reviewing the potential inhibitors/activators of this enzyme and their properties. [less ▲]

Low back pain including sciatica and DISH

in EULAR Compendium (2012)