Osteoarthritic chondrocytes undergo a glycolysis-related metabolic switch upon exposure to IL-1b or TNF.

BACKGROUND: Osteoarthritis is an age-related disease that currently faces a lack of symptomatic treatment. Inflammation, which is mainly sustained by pro-inflammatory cytokines such as IL-1b, TNF, and IL-6, plays an important role in osteoarthritis progression. In this context, pro-inflammatory cytokines are widely used to mimic the inflammatory component of osteoarthritis in vitro. However, the therapeutic failures of clinical trials evaluating anti-cytokines drugs highlight the lack of overall understanding of the effects of these cytokines on chondrocytes. METHODS: Here, we generated a comprehensive transcriptomic and proteomic dataset of osteoarthritic chondrocytes treated with these cytokines to describe their pro-inflammatory signature and compare it to the transcriptome of non-osteoarthritic chondrocytes. Then, the dysregulations highlighted at the molecular level were functionally confirmed by real-time cellular metabolic assays. RESULTS: We identified dysregulation of metabolic-related genes in osteoarthritic chondrocytes but not in non-osteoarthritic chondrocytes. A metabolic shift, toward increased glycolysis at the expense of mitochondrial respiration, was specifically confirmed in osteoarthritic chondrocytes treated with IL-1b or TNF. CONCLUSION: These data show a strong and specific association between inflammation and metabolism in osteoarthritic chondrocytes, which was not found in non-osteoarthritic chondrocytes. This indicates that the link between inflammation and metabolic dysregulation may be exacerbated during chondrocyte damage in osteoarthritis. Video Abstract.

Isokinetic knee strength deficit in patients with moderate haemophilia.

INTRODUCTION: Knee joint bleedings are responsible for quadriceps atrophy and strength deficit in patients with severe haemophilia. Little is known about patients with moderate haemophilia (PWMH). AIM: To evaluate isokinetic quadriceps and hamstrings strength in PWMH and to assess correlation with radiological and clinical parameter. METHODS: 18 PWMH aged 37.1 ± 11.4 and 18 healthy age-, weight- and height-matched controls performed a knee isokinetic test at 180°/s to assess quadriceps and hamstrings strength. In the PWMH group, knee Pettersson's score was pursued and Haemophilia Joint Health Score 2.1 (HJHS) was performed to determine unaffected knees (knee HJHS = 0) and affected ones (knee HJHS >0). RESULTS: Affected knees had a decrease of quadriceps strength compared to controls, 1.26 ± 0.47 vs 1.64 ± 0.27 Nm/kg and a decrease of hamstring strength, 0.60 ± 0.29 vs 1.03 ± 0.21 Nm/kg, (P < 0.001). Unaffected knees also had a decrease of quadriceps strength compared to controls, 1.36 ± 0.31 vs 1.64 ± 0.27 Nm/kg and a decrease of hamstring strength, 0.69 ± 0.18 vs 1.03 ± 0.21 Nm/kg, (P < 0.001). The conventional hamstring-to-quadriceps ratio was significantly decreased in affected knees compared to controls, 0.46 ± 0.15 vs 0.64 ± 0.13 (P < 0.001) but also in unaffected knees, 0.53 ± 0.16 vs 0.64 ± 0.13 (P = 0.02).No correlation was found between strength and HJHS or Pettersson's score. CONCLUSION: PWMH have a significant knee strength deficit, both on the quadriceps and the hamstrings, which is responsible for an important muscle imbalance.

A Comparison of Two Models Predicting the Presence of Chronic Exertional Compartment Syndrome.

Clinical history and physical examination are usually not sufficient to diagnose leg chronic exertional compartment syndrome (CECS). Two predictive clinical models have been proposed. The first model by De Bruijn et al. is displayed as a nomogram that predicts the probability of CECS according to a risk score. The second model by Fouasson-Chailloux et al. combines two signs (post-effort muscle hardness on palpation or hernia). To evaluate those models, we performed a prospective study on patients who were referred for possible CECS. 201 patients underwent intra-compartmental pressure at 1-min post-exercise (CECS if ≥ 30 mmHg) - 115 had CECS. For the De Bruijn et al. model, the risk score was 7.5±2.2 in the CECS group and 4.6±1.7 in the non-CECS group (p<0.001) with an area under the ROC curve of 0.85. The model accuracy was 80% with a sensitivity of 82% and a specificity of 78%. Concerning Fouasson-Chailloux et al. model, the accuracy was 86%; the sensitivity and the specificity were 75 and 98%, respectively. The De Bruijn et al. model was a good collective model but less efficient in individual application. In patients having both muscle hardness and hernia, we could clinically make the diagnosis of CECS.

Are corticosteroid injections needed after needling and lavage of calcific tendinitis? Randomised, double-blind, non-inferiority trial.

OBJECTIVE: Steroid injections are common after an ultrasound-guided puncture and lavage (UGPL) of calcific tendonitis of the rotator cuff. However, steroids may prevent calcification resorption and negatively affect tendon healing. Our study was designed to determine whether saline solution was non-inferior to steroids in the prevention of acute pain reactions in the week following UGPL. METHODS: This was a randomised, double-blinded, controlled non-inferiority trial with 12-month follow-up. We included 132 patients (66 in each group) with symptomatic calcification measuring more than 5 mm. Patients received 1 mL of saline or steroid (methylprednisolone 40 mg) in the subacromial bursa at the end of UGPL. Primary outcome was the maximal pain during the week following the procedure with a prespecified non-inferiority margin of 10 mm (0-100 visual analogue scale). Secondary outcomes included pain at rest and during activity, function (disabilities of the arm, shoulder and hand score) and radiological evolution of the calcification over the 12-month follow-up. RESULTS: The estimated mean difference in the first week's maximal pain between these two groups was 11.76 (95% CI 3.78 to 19.75). Steroids significantly improved VAS pain at rest and during activities, as well as function at 7 days and 6 weeks. They did not change the rate of calcification resorption, which occurred in 83% and 74% of patients at 12 months in the saline and steroid groups. CONCLUSION: Non-inferiority of saline when compared with steroids could not be established. However, steroid injection improved pain in the 6 weeks following the procedure, and function in the 3 months after, with no significant effect on calcification resorption. TRIAL REGISTRATION NUMBER: NTC02403856.

Pain catastrophising worsens RAPID3 in all rheumatologic conditions.

OBJECTIVES: To assess RAPID3 in various rheumatologic conditions, and the impact of pain catastrophising on RAPID3. METHODS: A set of questionnaires, including RAPID3 (0-30) and pain catastrophising score (0-52), was given to all outpatients seen in a one-month period: 518 patients fulfilled the questionnaires, including 127 RA (42% taking biologics), and 135 SpA (58% taking biologics). RESULTS: Mean pain catastrophising was 18.5±12.5, and 19% of patients could be classified as catastrophisers (>30). Higher RAPID3 scores were observed in the 33 osteoarthritis of lower limbs (16.44±5.20), 10 fibromyalgia (15.52±5.53), 47 back-pain (14.88±5.17), 17 osteoarthritis of upper limbs (13.61±7.42), and 38 tendinopathies (12.85±4.38). Lower RAPID3 were observed in the 135 SpA (12.79±6.03), 127 RA (12.18±6.30), 27 miscellaneous disorders (9.83±6.28), 7 entrapment neuropathies (9.81±4.51), 19 systemic connective tissue disorders (8.26±7.04) and 58 osteoporosis (7.85±6.95). Much higher RAPID3 scores were observed in the 19% with high pain catastrophising scores, whatever the conditions, and lower scores in the 15% with disablement benefits. RAPID3 was not associated with age or disease duration, but strongly correlated with daily fatigue, poor sleep, and length of daily pain. CONCLUSIONS: Thanks to progress made in RA and SpA treatment, higher RAPID3 scores were mostly observed in other rheumatic conditions, but co-morbidities and pain catastrophising might contribute to floor effects when assessing rheumatic disorders with RAPID3, hindering the recognition of low disease activity in some RA of SpA patients.

Bone Morphogenetic Protein 2 and Transforming Growth Factor ß1 Inhibit the Expression of the Proinflammatory Cytokine IL-34 in Rheumatoid Arthritis Synovial Fibroblasts.

IL-34 is a proinflammatory cytokine implicated in rheumatoid arthritis (RA). The current study aimed to assess the IL-34 expression in response to two members of the transforming growth factor (TGF)-ß family, TGF-ß1 and bone morphogenetic protein (BMP)-2, in synovial fibroblasts from RA patients. IL-34, TGF-ß1, and BMP-2 productions were measured in patient synovial fluids by enzyme-linked immunosorbent assay. IL-34 mRNA levels were quantified by real-time quantitative PCR in human synovial fibroblasts and murine mesenchymal stem cells. Pharmacologic inhibitions were used to determine the involvement of activin receptor-like kinase 1 (ALK1) and ALK5 downstream TGF-ß1 and BMP-2. IL-34, TGF-ß1, and BMP-2 were expressed in synovial fluids from RA patients. We found a significant correlation between IL-34 and TGF-ß1 expressions. Levels of both IL-34 and TGF-ß1 were thus correlated with the total leukocyte counts in the synovial fluids. TGF-ß1 and BMP-2 decreased IL-34 expression in the synovial fibroblasts or in murine mesenchymal stem cells in a dose- and time-dependent manner through ALK5 and ALK1 pathways, respectively. In addition, TGF-ß1 and BMP-2 antagonized tumor necrosis factor α-induced IL-34 gene expression. This work identifies TGF-ß1 and BMP-2 as potent inhibitors of IL-34 expression in RA synovial fibroblasts. These cytokines, as upstream inhibitors of IL-34, may thus contribute to antagonize inflammation and bone erosions in RA.

Multiple Vertebral Osteonecroses (Kümmell's Disease) After 10 Years on Denosumab: Is Osteocyte Apoptosis to Blame?

We report here a case of multiple vertebral osteonecroses with intrasomatic gaseous dissection (Kümmell's disease) occurring 1 year after the end of a 10-year course of denosumab treatment for osteoporosis without fractures. Histomorphometry and bone remodeling markers revealed major bone resorption and the persistence of an inhibition of bone formation. The presence of multiple empty lacunae in the bone provided evidence for high levels of osteocyte apoptosis. Osteocytes direct bone resorption (via the RANK/RANK-L/osteoprotegerin system) and formation (Wnt system, with SOST and DKK1) pathways. The vertebral osteonecrosis in our case may, therefore, have resulted from osteocyte apoptosis, decompensated by the sudden reactivation of bone remodeling after the cessation of denosumab treatment.

Detection of hypophosphatasia in hospitalised adults in rheumatology and internal medicine departments: a multicentre study over 10 years.

INTRODUCTION: Hypophosphatasia (HPP) is a rare genetic disease caused by loss-of-function mutations in the ALPL gene encoding the tissue non-specific alkaline phosphatase (ALP). Mild HPP is usually misdiagnosed in adult age. While an elevated serum ALP value draws more attention than a low value, low serum ALP should be better recognised and may lead to HPP detection. METHODS: Patients were selected from the records of the biochemistry department of six University Hospitals in France. Patients were hospitalised in the departments of rheumatology and internal medicine between 2007 and 2017. RESULTS: 56 321 hospitalised patients had at least 2 serum ALP dosages and 664 of these patients had at least 2 low serum ALP≤35 UI/L. Among these 664 patients, 482 (72.6%) had fluctuating low values (mean age 62.9 years; 60% of women) and 182 patients (27.4%) had persistent low values below 35 IU/L (mean age 53.4 years; 67% of women). Among patients with persistent hypophosphatasaemia treated with bisphosphonates, 70.8% never had ALP measurement before treatment and 20.8% were treated despite an abnormal decrease of ALP. Genetic testing was performed in 18 patients and was positive in 11. Genetic diagnosis of HPP was at least 6.0% in persistent hypophosphatasaemia and at least 15.9% in patients with at least three symptoms suggestive of HPP. CONCLUSION: In this 10-year retrospective study, 0.32% of adult patients hospitalised in the rheumatology and internal medicine departments had persistently low serum ALP, and among them, 6% had genetically proven HPP. Reported hypophosphatasaemia represented only 3.6% of hospitalised patients.

Effect of adding bone marrow to ceramic graft materials with different interconnectivities in lumbar arthrodesis : quantification of bone formation.

INTRODUCTION: Combining bone marrow (BM) with graft materials can stimulate bone healing. However, bone growth is not quantified in most studies, and the influence of the rate of interconnectivity of ceramics loaded with bone marrow has not yet been quantified. Here, a rabbit model of posterolateral intertransverse arthrodesis was used to quantify the effect of adding BM to partially (PIC) or totally (TIC) interconnected ceramics. MATERIALS AND METHODS: A single lumbar level was grafted on two sides with TIC (n = 12) or PIC (n = 18). The ceramic was loaded with 1.5 ml of BM on one side (chosen at random). The fusion rate was assessed by manual palpation test. Bone formation was quantified on scanning electron microscopy images and by dual-energy X-ray absorptiometry. RESULTS: At week 6, bone formation with TIC was twice as high as that with PIC. When BM was added, 35.1 and 87.8 % more bone formation was observed in the TIC and PIC, respectively. In ceramics loaded with BM, the bone mineral density was significantly higher than that in ceramics alone. CONCLUSIONS: Differences in interconnectivity within the family of biphasic ceramics should be taken into account when applying them clinically. BM increased bone formation regardless of the type of ceramic employed.

Musculoskeletal corticosteroid injections: Recommendations of the French Society for Rheumatology (SFR).

Musculoskeletal corticosteroid injections are widely performed, although the exact practice varies greatly due to advances in knowledge and techniques. This justifies updating and drawing up good practice recommendations. Using a consensus model formalized by the French National Authority for Health (HAS) and based on a literature review that resulted in a "white book", 13 recommendations were developed by a group of experts. These recommendations were then sent online to 48 specialists for evaluation, 27 of whom were rheumatologists and 15 of whom were general practitioners. These recommendations were also presented at the 34th annual meeting of the French Society for Rheumatology (SFR) (Paris, December 2021) at a symposium attended by a hundred or so rheumatologists, who voted on these recommendations in person. The results are presented as an overall score out of 10, a median out of 10 and as tertiles. The agreement was excellent for 10 of these 13 recommendations, with mean values of 8.5 to 9.1 out of 10, median values of 9 or 10 out of 10 and agreement of 91.7% to 97.9%, which corresponds to a consensus. The 3 other recommendations were broadly supported but were the subject of more debate. One relates to patient information (mean 7.3/10, median 8/10, upper tertile 72.9%) with discussion about the waiting period. Another related to the summary report (mean 8.4/10, median 9, upper tertile 91.7%) with discussions about its content and the need to specify the lot number of the injected product. The last one related to periprosthetic injections and the need to consult and get approval from a specialist (mean 8.0/10, median 8, upper tertile 83.3%) with mostly the general practitioners having reservations. In all, there is a very strong consensus among the musculoskeletal corticosteroid injection experts and specialists consulted, which justifies them being taken into consideration to improve our daily practice.

Harnessing cell-material interactions to control stem cell secretion for osteoarthritis treatment.

Osteoarthritis (OA) is the most common debilitating joint disease, yet there is no curative treatment for OA to date. Delivering mesenchymal stromal cells (MSCs) as therapeutic cells to mitigate the inflammatory symptoms associated with OA is attracting increasing attention. In principle, MSCs could respond to the pro-inflammatory microenvironment of an OA joint by the secretion of anti-inflammatory, anti-apoptotic, immunomodulatory and pro-regenerative factors, therefore limiting pain, as well as the disease development. However, the microenvironment of MSCs is known to greatly affect their survival and bioactivity, and using tailored biomaterial scaffolds could be key to the success of intra-articular MSC-based therapies. The aim of this review is to identify and discuss essential characteristics of biomaterial scaffolds to best promote MSC secretory functions in the context of OA. First, a brief introduction to the OA physiopathology is provided, followed by an overview of the MSC secretory functions, as well as the current limitations of MSC-based therapy. Then, we review the current knowledge on the effects of cell-material interactions on MSC secretion. These considerations allow us to define rational guidelines for next-generation biomaterial design to improve the MSC-based therapy of OA.

Click and bioorthogonal hyaluronic acid hydrogels as an ultra-tunable platform for the investigation of cell-material interactions.

The cellular microenvironment plays a major role in the biological functions of cells. Thus, biomaterials, especially hydrogels, which can be design to mimic the cellular microenvironment, are being increasingly used for cell encapsulation, delivery, and 3D culture, with the hope of controlling cell functions. Yet, much remains to be understood about the effects of cell-material interactions, and advanced synthetic strategies need to be developed to independently control the mechanical and biochemical properties of hydrogels. To address this challenge, we designed a new hyaluronic acid (HA)-based hydrogel platform using a click and bioorthogonal strain-promoted azide-alkyne cycloaddition (SPAAC) reaction. This approach facilitates the synthesis of hydrogels that are easy to synthesize and sterilize, have minimal swelling, are stable long term, and are cytocompatible. It provides bioorthogonal HA gels over an uncommonly large range of stiffness (0.5-45 kPa), all forming within 1-15 min. More importantly, our approach offers a versatile one-pot procedure to independently tune the hydrogel composition (e.g., polymer and adhesive peptides). Using this platform, we investigate the independent effects of polymer type, stiffness, and adhesion on the secretory properties of human adipose-derived stromal cells (hASCs) and demonstrate that HA can enhance the secretion of immunomodulatory factors by hASCs.

Rheumatoid arthritis and sexuality: a patient survey in France.

BACKGROUND: The objective of this study was to evaluate the impact of rheumatoid arthritis (RA) on patients' sexuality and identify disease and other factors such as fatigue that most influence sexual relationships. METHODS: A specific pretested questionnaire was sent to all members of a French patient association (ANDAR). Questions related to demographics, disease status, quality of life (utility, EQ-5D), pain, psychological status (mood), fatigue and emotional and sexual relationships. To isolate the impact of RA, an attempt was made to include a matched sample from the general population. RESULTS: The analysis included 1271 patients, but only 70 controls agreed to participate and comparisons should therefore be considered with caution. The two groups were similar in terms of age, gender distribution, living conditions and diseases other than RA. However, patients scored worse for global health, mood, fatigue, had a lower utility (0.55 versus 0.65). Controls were more active sexually (69% versus 63%), in particular women (71% versus 60%). Age, gender, living alone, physical function and mood were significant predictors for being sexually active for patients; for controls, age and overall quality of life (utility) were significant predictors. CONCLUSIONS: While it is known that RA has a negative impact on patients' sexuality, there have been few attempts to quantify the problem. Our study highlights the negative impact of RA on patients' sexuality, and triggers the question how to include this aspect into care.

Relationships between bone mass and micro-architecture at the mandible and iliac bone in edentulous subjects: a dual X-ray absorptiometry, computerised tomography and microcomputed tomography study.

OBJECTIVES: To compare bone volume, bone mineral density, cortical thickness and bone micro-architecture in a series of paired mandibular and iliac bone samples analysed by various imagery techniques to see whether relationships exist between the various techniques and between mandibular and iliac bone. MATERIALS AND METHODS: Bone samples from the mandible and ilium were harvested in 20 cadavers and analysed by dual energy X-ray absorptiometry (DXA), computerised tomography (CT) on a conventional hospital machine and microCT. RESULTS: Significant correlations were found between Hounsfield density obtained by CT, and bone mass determined by microCT but not with DXA values. Cortical thickness measurements were well correlated between CT and microCT. No relationships were found between mandibular and iliac bone, when considering mineral density, cortical thickness, bone volume or micro-architecture. CONCLUSION: In clinical practice, CT remains the most appropriate routine means for bone qualitative and quantitative evaluation at the mandible. In this ex vivo study, these results confirm that mandibular bone status does not reflect the axial skeletal one and assist in the placement of implants with dental prostheses in old or osteoporotic patients.

Gait Alteration Due to Haemophilic Arthropathies in Patients with Moderate Haemophilia.

Some patients with moderate haemophilia (PWMH) report joint damage potentially responsible for gait disorders. Three-dimensional gait analysis (3DGA) is a relevant tool for the identification of complex musculoskeletal impairment. We performed an evaluation with 3DGA of 24 PWMH aged 44.3 ± 16.1 according to their joint status [Haemophilia Joint Health Score (HJHS) < 10 or HJHS ≥ 10] and assessed the correlation with the radiological and clinical parameters. Sixteen had HJHS < 10 (group 1) and eight had HJHS ≥ 10 (group 2). They were compared to 30 healthy subjects of a normative dataset. Both knee and ankle gait variable scores were increased in group 2 compared to the controls (p = 0.02 and p = 0.04, respectively). The PWMH of group 2 had a significant increase in their stance phase, double support duration, and stride width compared to the controls and group 1 (p < 0.01). Very low correlations were found for the ankle gait variable score with the ankle Pettersson sub-score (r2 = 0.250; p = 0.004) and ankle HJHS sub-score (r2 = 0.150; p = 0.04). For the knee, very low correlation was also found between the knee gait variable score and its HJHS sub-score (r2 = 0.290; p < 0.0001). Patients with moderate haemophilia presented a gait alteration in the case of poor lower limb joint status.

Efficacy of a nurse-led patient education intervention in promoting safety skills of patients with inflammatory arthritis treated with biologics: a multicentre randomised clinical trial.

OBJECTIVE: To evaluate the effect of a nurse-led patient education on safety skills of patients with inflammatory arthritis treated with biologic disease-modifying antirheumatic drugs (bDMARDs). METHODS: This is a multicentre, open-labelled, randomised controlled trial comparing an intervention group (face-to-face education by a nurse at baseline and 3 months later) with a control group (usual care) at the introduction of a first subcutaneous bDMARD. The primary outcome was score on the BioSecure questionnaire at 6 months (0-100 scale), a validated questionnaire assessing competencies in dealing with fever, infections, vaccination and daily situations. The secondary outcomes were disease activity, coping, psychological well-being, beliefs about medication, self-efficacy and severe infection rate. RESULTS: 129 patients with rheumatoid arthritis and spondyloarthritis were enrolled in nine rheumatology departments; 122 completed the study; 127 were analysed; and 64 received the intervention (mean duration: 65 min at baseline and 44 min at 3 months). The primary outcome was met: the BioSecure score was 81.2±13.1 and 75.6±13.0 in the education and usual care groups (difference: +6.2, 95% CI 1.3 to 11.1, p=0.015), demonstrating higher safety skills in the education group. Exploratory analyses showed better skills regarding infections, greater willingness for vaccinations and greater adherence-related behaviours in the education group. Coping was significantly more improved by education; other secondary outcomes were improved in both groups, with no difference. CONCLUSIONS: Educating patients was effective in promoting patient behaviours for preventing adverse events with bDMARDs. An education session delivered to patients starting a first bDMARD can be useful to help them self-manage safety issues. TRIAL REGISTRATION NUMBER: NCT02855320.

Ultrasound assessment of the posterior sacroiliac ligaments.

OBJECTIVES: Posterior ligaments of the sacroiliac joints (SIJ) are comprised of the long and the short posterior sacroiliac ligaments. They are recognised as a potential source of aspecific low back pain or peripartum pelvic pain. The aim of this study was to assess the characteristics of these ligaments using high resolution ultrasonography (HRUS). METHODS: The features of the ligaments was first studied in a formalin-preserved intact cadaver. US characteristics were then recorded in 20 volunteers with a Philips HD11 XE unit using a multifrequency linear transducer (5-12 Mhz). RESULTS: US was performed in 8 men and 12 women, with a mean age of 45±15 year and mean body mass index (BMI) of 25.45 (±3.57). Ligaments were identified in all the volunteers. The short posterior sacroiliac ligament (median length 2.17 cm and 2.31 cm in the right and left SIJ respectively) was described as a fibrilar structure attached to the posterior tuberosity of the ilium and the sacrum. The long posterior sacroiliac ligament (median length 3.42 cm and 3.56 cm in the right and left SIJ, respectively) was a fibrilar structure attached superiorly to the posterior superior iliac spine and inferiorly to the third sacral transverse tubercle. CONCLUSIONS: Our study shows that US can be used to identify the posterior ligaments of the sacroiliac joint. US could be useful to detect any pathological change associated with pain and to guide steroid injection in these ligaments.

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.