Bone sialoprotein as a potential key factor implicated in the pathophysiology of osteoarthritis.

OBJECTIVE: We previously identified an association between bone sialoprotein (BSP) and osteoarthritic (OA) chondrocyte hypertrophy but the precise role of BSP in ostearthritis (OA) has not been extensively studied. This study aimed to confirm the association between BSP and OA chondrocyte hypertrophy, to define its effect on molecules produced by chondrocytes and to analyse its association with cartilage degradation and vascular density at the osteochondral junction. METHOD: Human OA chondrocytes were cultivated in order to increase hypertrophic differentiation. The effect of parathyroid hormone-related peptide (PTHrP), interleukin (IL)-1ß or tumour necrosis factor (TNF)-α on BSP was analysed by real-time reverse transcription polymerase chain reaction (RT-PCR) and western blot. The effects of BSP on OA chondrocytes production of inflammatory response mediators (IL-6, nitric oxide), major matrix molecule (aggrecan), matrix metalloprotease-3 and angiogenic factors (vascular endothelial growth factor, basic fibroblast growth factor, IL-8, and thrombospondin-1) were investigated. BSP was detected by immunohistochemistry and was associated with cartilage lesions severity and vascular density. RESULTS: PTHrP significantly decreased BSP, confirming its association with chondrocyte hypertrophy. In presence of IL-1ß, BSP stimulated IL-8 synthesis, a pro-angiogenic cytokine but decreased the production of TSP-1, an angiogenesis inhibitor. The presence of BSP-immunoreactive chondrocytes in cartilage was associated with the severity of histological cartilage lesions and with vascular density at the osteochondral junction. CONCLUSION: This study supports the implication of BSP in the pathology of OA and suggests that it could be a key mediator of the hypertrophic chondrocytes-induced angiogenesis. To control chondrocyte hypertrophic differentiation is promising in the treatment of OA.

Consequences of chondrocyte hypertrophy on osteoarthritic cartilage: potential effect on angiogenesis.

OBJECTIVE: The aim of this study was to investigate the link between the hypertrophic phenotype of chondrocytes and angiogenesis in osteoarthritis (OA) and more particularly to demonstrate that OA hypertrophic chondrocytes potentially express a phenotype promoting angiogenesis through the expression of factors controlling endothelial cells migration, invasion and adhesion. METHOD: Human OA chondrocytes were cultivated in alginate beads in medium supplemented with 10% fetal bovine serum (FBS) to induce chondrocyte hypertrophy. The hypertrophic phenotype was characterized throughout 28 days of culture by measuring the expression of specific genes and by a microscopic observation of cellular morphology. The effect of media conditioned by OA hypertrophic chondrocyte on endothelial cells migration, invasion and adhesion was evaluated in functional assays. Moreover, hypertrophic OA chondrocytes were tested for the expression of angiogenic factors by real-time RT-PCR. RESULTS: Specific markers of hypertrophy and observation of cellular morphology attested of the hypertrophic phenotype of chondrocytes in our culture model. Functional angiogenesis assays showed that factors produced by hypertrophic chondrocytes stimulated migration, invasion and adhesion of endothelial cells. Among the evaluated angiogenic factors, bone sialoprotein (BSP) was the most highly upregulated in hypertrophic chondrocytes. The inhibition of endothelial cell adhesion by a GRGDS peptide confirmed the implication of RGD domain proteins, like BSP, in hypertrophic chondrocyte-induced adhesion of endothelial cells. CONCLUSION: Hypertrophic differentiation of chondrocyte may promote angiogenesis. Our findings established the relation of BSP with OA chondrocyte hypertrophy and suggested that this factor could constitute a potential target to control cartilage neovascularisation in OA.

Phenotypic characterization of osteoblasts from the sclerotic zones of osteoarthritic subchondral bone.

OBJECTIVE: To determine the phenotype of osteoblasts from the sclerotic zones of human osteoarthritic (OA) subchondral bone. METHODS: Human osteoblasts were isolated from sclerotic or nonsclerotic areas of subchondral bone and cultured for 14 days in monolayer. The expression of 14 genes was investigated by real-time reverse transcription-polymerase chain reaction. The activities of alkaline phosphatase (AP) and transglutaminases (TGases) were quantified by enzymatic assays. C-terminal type I procollagen propeptide (CPI), interleukin-1beta (IL-1beta), IL-6, IL-8, transforming growth factor beta1 (TGFbeta1), osteocalcin (OC), and osteopontin (OPN) were assayed in the culture medium by immunoassay. RESULTS: Gene expression levels of matrix metalloproteinase 13, COL1A1 and COL1A2, OPN, tissue-nonspecific AP, OC, vascular endothelial growth factor, ANKH, TGase 2, factor XIIIA, and dentin matrix protein 1 were significantly up-regulated in sclerotic osteoblasts compared with nonsclerotic osteoblasts. In contrast, parathyroid hormone receptor gene expression was depressed in sclerotic osteoblasts, but bone sialoprotein levels were unchanged. The activities of AP and TGases were increased in sclerotic osteoblasts, while matrix mineralization, revealed by alizarin red staining, was decreased. In parallel, protein synthesis of CPI, OC, OPN, IL-6, IL-8, and TGFbeta1 was significantly higher in sclerotic osteoblasts than in nonsclerotic osteoblasts, while IL-1beta production was similar in both groups. CONCLUSION: These findings contribute to a better understanding of the mechanisms involved in subchondral bone sclerosis and identify osteoblasts with an altered phenotype as a potential target for future OA therapies.

[Role of standard radiography and computed tomography in the assessment of shoulder instability: decision-making value in surgical planning. (Radio-anatomic study of 51 unstable shoulders)]. / Place de la radiographie standard et de l'arthroscanner dans le bilan préopératoire des instabilités d'épaule: valeur décisionnelle dans l'approche chirurgicale. (Etude radio-anatomique sur 51 épaules instables).

The therapeutic algorythm for shoulder instability, either arthroscopically, either surgically, should focus on clinical data as well as imaging ones. The latter involve standard X-rays and arthrotomodensitometry (AOTDM). Both of these are crucial for the surgical approach. This paper emphasizes their limits and places. We analysed anatomical and imaging data of 51 unstable shoulders operated on between January 1998 and February 2000. Our purpose was to determine the sensitivity and specificity of imaging techniques for each anatomical structure playing a role in the management. Standard X-rays include comparative AP and Bernageau's views. Based on our results, their efficiency is confirmed for the therapeutic approach of bony lesions. Their sensitivity was respectively 96% and 93% for the reconnaissance of Hill-Sachs lesions and lesions of the anterior glenoïd rim. The sensitivity of AOTDM in identifying labral desinsertions was 91% but their extent was not precisely documented likewise for the labral degeneration and absence. The sensitivity was respectively 69% and 71%. Results were poor for the evaluation of the anterior ligament complex. TDM could not accurately document 90% soft tissues lesions which carry a poor prognosis for arthroscopic reconstructive procedures. There is a good correlation between the aspect of anterior capsular attachment and the sprain lesions (P = 0.003). We could conclude that the AOTDM is not determinant factor for choice of the reconstructive procedure, either arthroscopically, either surgically.