Characterization of the age-dependent intervertebral disc changes in rabbit by correlation between MRI, histology and gene expression.

BACKGROUND: The present study was conducted to address whether the intervertebral disc of rabbit could be considered (i) as a valuable model to provide new insights into the tissue and cellular changes of Nucleus pulposus aging and (ii) as an appropriate tool to investigate the efficacy of Nucleus pulposus cell-based biotherapies. METHODS: Lumbar intervertebral disc from rabbits with increasing ages (1, 6 and 30 month-old) were compared by MRI and histological observation using Pfirrmann's grading and Boos' scoring respectively. The expression of transcripts (COL2A1, AGC1, COL1A1, MMP13, BMP2, MGP and p21) in Nucleus pulposus cells were analysed by quantitative real-time PCR. RESULTS: MRI analysis indicated an early age-dependent increase in the Pfirrmann's grading. Histological Boos' scoring was also increased. The analysis of transcript expression levels showed that COL2A1 and AGC1 were down-regulated as a function of age. Conversely, COL1A1, MMP-13, BMP-2, MGP and p21 were significantly up-regulated in the Nucleus pulposus cells of aged rabbit intervertebral disc. CONCLUSIONS: Our study describes the consistency of the rabbit as a model of intervertebral disc changes as a function of age by correlating tissue alteration with cellular modification measured.

Identification of phenotypic discriminating markers for intervertebral disc cells and articular chondrocytes.

OBJECTIVE: The present study was conducted to improve our knowledge of intervertebral disc (IVD) cell biology by comparing the phenotype of nucleus pulposus (NP) and annulus fibrosus (AF) cells with that of articular chondrocytes (ACs). METHODS: Rabbit cells from NP and AF were isolated and their phenotype was compared with that of AC by real-time PCR analysis of type I (COL1A1), II (COL2A1) and V (COL5A1) collagens, aggrecan transcript (AGC1), matrix Gla protein (MGP) and Htra serine peptidase 1 (Htra1). RESULTS: Transcript analysis indicated that despite certain similarities, IVD cells exhibit distinct COL2A1/COL1A1 and COL2A1/AGC1 ratios as compared with AC. The expression pattern of COL5A1, MGP and Htra1 makes it possible to define a phenotypic signature for NP and AF cells. CONCLUSIONS: Our study shows that NP and AF cells exhibit a clearly distinguishable phenotype from that of AC. Type V collagen, MGP and HtrA1 could greatly help to discriminate among NP, AF and AC cells.

Randomised study versus control group of customised therapeutic education for patients in follow-up for rheumatoid arthritis.

OBJECTIVE: We have evaluated customized objectives, predefined during a therapeutic education session for rheumatoid arthritis (RA). METHODS: Fifty-four RA patients were randomised into patient therapeutic education (PTE) group versus waiting list (WL). The final comparative evaluation involved solving 3 predefined problems. RESULTS: Fifty-four were evaluated after 6 months. The main criterion was defined for all three of the chosen themes at 76.9% in the PTE group and 42.4% in the WL group. Among the other positively evaluated criteria were: less corticotherapy, more occupational therapy, more demand for social aid, more physical activity, knowledge of the recognition of an RA attack and how to cope with it. On the other hand, knowledge of the treatments did not differ between the 2 groups nor did the RAPID scores, fatigue, stiffness, depression, compliance, number of consultations and hospitalisations. Patient satisfaction was excellent (between 85.3 and 93.9%). CONCLUSION: This study is a good illustration of the position occupied and value of PTE in solving the problems specific to each RA case, the resulting high level of patient satisfaction and its independently complementary aspects relative to the purely medical treatment of RA. Customized PTE could better respond to specific patients problems in RA.

Information on glucocorticoid therapy in the main studies of biological agents.

OBJECTIVE: To evaluate reported information on prednisone therapy in the main studies of biological agents used to treat rheumatoid arthritis (RA). METHODS: We reviewed 66 publications (including four abstracts), including 11 studies of infliximab, 19 of etanercept, eight of adalimumab, five of golimumab, four of certolizumab, four of rituximab, eight of abatacept, and seven of tocilizumab. RESULTS: Whether concomitant prednisone therapy was used, it was specified in only 56 (85%) of the 66 publications. Only 42 (64%) publications indicated that the prednisone dosage remained unchanged throughout the study. The maximum prednisone dosage allowed was specified in only 39 (59%) reports and was lower than 8 mg/day in only four (6%) studies. Data enabling determination of the mean daily prednisone dosage in prednisone-treated patients was available for only eight (12%) studies; the mean dosage ranged from 5.0 to 9 mg/day (mean, 7.1 ± 1.5). The percentage of patients receiving prednisone therapy was reported for only 41 (62%) studies. All the above-mentioned information was available in only two (3%) study reports. The percentage of patients on prednisone therapy ranged from 34% to 93% (mean, 58 ± 13%) overall and varied across biological agents as follows: abatacept, 74.4%; golimumab, 67.9%; infliximab, 60.6%; certolizumab, 57.5%; rituximab, 57.5%; etanercept, 54.4%; tocilizumab, 52.8%; and adalimumab, 50.4%. These percentages did not decline between 1997 and 2010. CONCLUSION: Study reports provide inadequate information on prednisone therapy during biological treatment for RA.

From osteoarthritis treatments to future regenerative therapies for cartilage.

Osteoarthritis (OA) is associated with cartilage degeneration and an accompanying inflammatory syndrome of the synovium in addition to alteration of the subchondral bone. The molecular and cellular events involved in OA have only partially been elucidated. This review provides a global view of the physiopathology of OA, as well as non-pharmacological and pharmacological treatments for the disorder. An update on surgical treatments and their indications is given with an orientation towards the management of OA and cartilage repair by cell-based regenerative therapies. These promising biological technologies will, potentially, play a major role in the treatment of cartilage-associated diseases.