Effects of Ceramide on Apoptosis, Proteoglycan Degradation, and Matrix Metalloproteinase Expression in Rabbit Articular Cartilage

Sabatini, Massimo; Rolland, Gaëlle; Léonce, Stéphane; Thomas, Mireille; Lesur, C.; Pérez, Valérie; Nanteuil, Guillaume De; Bonnet, Jacqueline

doi:10.1006/bbrc.1999.1983

Cited by 59 publications

(58 citation statements)

References 36 publications

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“…Studies of articular cartilage suggest that ceramide plays a role in cartilage degeneration and the disruption of cartilage matrix homeostasis to decrease the levels of type II collagen (65,66). Farber disease, in which a lack of ceramidase causes excess ceramide accumulation within the cartilage and bone, is associated with arthritis-like joint degeneration (67).…”

Section: Discussionmentioning

confidence: 99%

Bone Morphogenic Protein (BMP) Signaling Up-regulates Neutral Sphingomyelinase 2 to Suppress Chondrocyte Maturation via the Akt Protein Signaling Pathway as a Negative Feedback Mechanism

Kakoi

Maeda

Shinohara

et al. 2014

Journal of Biological Chemistry

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Background: It is not clear how BMP-induced chondrocyte maturation is cell-autonomously terminated. Results: BMP-2 induced the ceramide-generating enzyme neutral sphingomyelinase 2 (nSMase2) in chondrocytes, whereas silencing of nSMase2 enhanced maturation in an Akt signaling-dependent manner. Conclusion: nSMase2 signaling regulates BMP-induced chondrocyte maturation as a negative feedback mechanism. Significance: This study elucidated the novel link between BMP and lipid signaling in chondrogenesis.

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Section: Discussionmentioning

confidence: 99%

Bone Morphogenic Protein (BMP) Signaling Up-regulates Neutral Sphingomyelinase 2 to Suppress Chondrocyte Maturation via the Akt Protein Signaling Pathway as a Negative Feedback Mechanism

Kakoi

Maeda

Shinohara

et al. 2014

Journal of Biological Chemistry

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“…The apoptotic cell rate range is 3-10% in intact articular cartilage in adult rats and mice [1]. Enhanced chondrocyte apoptosis can cause imbalances in the levels of matrix metalloproteinase and its inhibitor derived from an affected synovial membrane [7,20,23], and in proinflammatory responses [12]. In acute and subacute phases after injury, inflammatory cytokines are thought to affect chondrocyte apoptosis and matrix degradation [12,24].…”

Section: Discussionmentioning

confidence: 99%

“…A mechanical load is necessary on the formation, degradation, regeneration and tissue composition of tendons, ligaments and cartilage [9-11, 13, 17]. In a rabbit articular cartilage in osteoarthritis, proteoglycan degradation and matrix metalloproteinase expression were reported [23]. Persistent mechanical stress deprivation and/or proteinases could induce histological changes of insertion site in the resected group.…”

Section: Discussionmentioning

confidence: 99%

Chondrocyte Apoptosis and Decrease of Glycosaminoglycan in Cranial Cruciate Ligament Insertion after Resection in Rabbits

Hattori

Sakane

Mutsuzaki

et al. 2007

The Journal of Veterinary Medical Science

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ABSTRACT. We examined time-dependent histological changes of the calcified fibrocartilage area in a tibial cranial cruciate ligament (CCL) insertion after ligament resection in rabbits. The animals were divided into two groups: those undergoing CCL substance resection in the right stifle (resected group) and those receiving the same operation without CCL resection in the left stifle (sham operated group). Five animals were euthanized with deep anaesthesia at four time periods (1, 2, 4 and 6 weeks), and Haematoxylin-eosin and Safranin-O stainings and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) staining were performed. The average percentage of TUNEL-positive chondrocytes and the average thickness of the glycosaminoglycan (GAG)-stained area in the calcified fibrocartilage area were measured. Two and 4 weeks after the surgery, the average percentages of TUNELpositive chondrocytes in the resected group (23.8 ± 10.3% and 15.9 ± 6.7%, respectively) were significantly higher than those in the sham operated group (8.9 ± 3.8% and 7.4 ± 1.6%, P<0.05, respectively). Six weeks after the surgery, the average thickness of the GAGstained area in the resected group (7.7 ± 13. 5µm) was significantly smaller than that in the sham operated group (69.4 ± 39.9 µm, P<0.05). Our results suggest that the average percentage of TUNEL-positive chondrocytes became a peak in 2 weeks and that histological changes occurred in 6 weeks. The chondrocyte apoptosis can induce decrease of GAG-stained area after resection of CCL. Therefore, chondrocyte apoptosis in the calcified cartilage area in the CCL tibial insertion might lead to histological changes. KEY WORDS: apoptosis, cranial cruciate ligament, insertion.J. Vet. Med. Sci. 69(3): 253-258, 2007 The cranial cruciate ligament (CCL) is one of the intraarticular ligaments of the stifle joint that connects the femur and tibia (equivalent of anterior cruciate ligament, ACL in human). The CCL insertion site consists of 4 distinguishable tissue zones of transition, that is, ligaments, uncalcified fibrocartilage, calcified fibrocartilage, and bone [6,8,28]. Gradual hardness changes of different tissues reduce stress concentration at the insertion site [6,28]. Containing glycosaminoglycan (GAG) in the cartilage zone provides water absorbability and flexibility to the ligament [5]. GAG and fibrocartilage layers are presumed to resist shear stress at the insertion site [28]. A mechanical load is necessary to produce cartilage layers and GAG at the insertion site of ligaments and tendons [5,14,22].In humans, traffic accidents or sports activities sometimes cause knee ligament injuries such as an injury to ACL. Many dogs also rupture or tear CCL due to their physical action [27]. In humans after rupturing ACL, the early reformation of synovial tissue over the ends of the ligament combined with the formation of myofibroblast-like cells with contractible properties in this synovial tissue might be responsible in part for the retraction of the ...

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“…This is the first study to demonstrate that C2-ceramide inhibits proliferation and induces apoptosis in growth plate chondrocytes. Ceramide has been shown to induce apoptosis in a wide range of different cell types, including pancreatic b-cells (Sjoholm 1995), cardiomyocytes (de Vries et al 1997), astrocytes (Oh et al 2006) and articular chondrocytes (Sabatini et al 2000, Gilbert et al 2004.…”

Section: Discussionmentioning

confidence: 99%

“…Ceramide has also been shown to induce apoptosis in a wide range of different cell types, including pancreatic b-cells (Sjoholm 1995), cardiomyocytes (de Vries et al 1997 and astrocytes (Oh et al 2006). Furthermore, ceramide has been shown to induce apoptosis, proteoglycan degradation and matrix metalloproteinase expression in articular chondrocytes (Sabatini et al 2000, Gilbert et al 2004.…”

Section: Introductionmentioning

confidence: 99%

Ceramide inhibition of chondrocyte proliferation and bone growth is IGF-I independent

MacRae¹,

Burdon²,

Ahmed³

et al. 2006

Journal of Endocrinology

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Proinflammatory cytokines inhibit growth plate development. However, their underlying mechanisms of action are unclear. These effects may be mediated by ceramide, a sphingosine-based lipid second messenger, which is elevated in a number of chronic inflammatory diseases. To test this hypothesis, we determined the effects of C2-ceramide, a cell permeable ceramide analogue, on the growth of the ATDC5 chondrogenic cell line and on cultured fetal mice metatarsals. In ATDC5 cells, C2-ceramide significantly induced apoptosis at both 40 (82%; P!0 . 05) and 25 mM (53%; P!0 . 05). At 40 mM, C2-ceramide significantly reduced proliferation ([ 3 H]-thymidine uptake/mg protein) (62%; P!0 . 05). C2-ceramide did not markedly alter the differentiation state of the cells as judged by the expression of markers of chondrogenesis and differentiation (sox 9, collagen II and collagen X). The IGF-I signalling pathway is the major autocrine/paracrine regulator of bone growth. Both in the presence and absence of IGF-I, C2-ceramide (25 mM) induced an equivalent reduction in proliferation (60%; P!0 . 001). Similarly, C2-ceramide (40 mM) induced a 31% reduction in fetal metatarsal growth both in the presence and absence of IGF-I (both P!0 . 001). Furthermore, C2-ceramide reduced ADCT5 proliferation in the presence of AG1024, an IGF-I and insulin receptor blocker. Therefore, C2-ceramide-dependent inhibition appears to be independent of IGF-mediated stimulation of bone growth. Indeed, biochemical studies demonstrated that C2-ceramide (25 mM) pretreatment did not alter IGF-I-stimulated phosphorylation of insulin receptor substrate-1, Akt or P44/42 MAP kinase. In conclusion, C2-ceramide inhibits proliferation and induces apoptosis in growth plate chondrocytes through an IGF-I independent mechanism.

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Effects of Ceramide on Apoptosis, Proteoglycan Degradation, and Matrix Metalloproteinase Expression in Rabbit Articular Cartilage

Cited by 59 publications

References 36 publications

Bone Morphogenic Protein (BMP) Signaling Up-regulates Neutral Sphingomyelinase 2 to Suppress Chondrocyte Maturation via the Akt Protein Signaling Pathway as a Negative Feedback Mechanism

Bone Morphogenic Protein (BMP) Signaling Up-regulates Neutral Sphingomyelinase 2 to Suppress Chondrocyte Maturation via the Akt Protein Signaling Pathway as a Negative Feedback Mechanism

Chondrocyte Apoptosis and Decrease of Glycosaminoglycan in Cranial Cruciate Ligament Insertion after Resection in Rabbits

Ceramide inhibition of chondrocyte proliferation and bone growth is IGF-I independent

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