Articular Function Research Articles

Double-Needle Arthrocentesis with Viscosupplementation in Patients with Temporomandibular Joint Disc Displacement without Reduction

OBJECTIVES:Arthrocentesis is the simplest surgical intervention for the temporomandibular joint (TMJ). It can be performed on an outpatient basis at a low cost and with low morbidity. The objective is to release the articular disc by disrupting the adhesion formed between its surfaces and the mandibular fossa through hydraulic pressure generated by irrigation of the upper compartment of the TMJ. Viscosupplementation with hyaluronic acid during or after arthrocentesis improves clinical outcomes, increases mouth opening, and reduces pain levels. The aim of this study was to evaluate the efficiency of arthrocentesis plus hyaluronic acid viscosupplementation through clinical examination and preoperative magnetic resonance imaging in patients with unilateral disc displacement without reduction (DDwoR).METHODS:This analytical retrospective cross-sectional study clinically and radiologically evaluated 72 patients of both sexes with unilateral DDwoR. The following data were collected: sex, pain, age, duration of pain, maximum mouth opening, and patient pain perception on a visual analog scale. TMJ arthrocentesis was performed only once for each of the indicated joints. Data were collected before arthrocentesis (baseline) and at 7, 14, 30, 60, 90, and 180 days after the procedure (final evaluation).RESULTS:Between the baseline and final evaluation, there was a significant reduction in pain (p=0.001) and restoration of articular function. In addition, there was a significant increase in maximum mouth opening (p=0.001).CONCLUSION:Patients with DDwoR undergoing arthrocentesis combined with hyaluronic acid injection showed significant improvement in the perceived pain and maximum mouth opening in the mid-term follow-up periods.

Functional outcome of patients treated with proximal humeral internal locking osteosynthesis plate in proximal humeral fractures

<p class="abstract"><strong>Background:</strong> Displaced or unstable proximal humeral fractures fare poorly with non-operative treatment. These are better treated with surgical intervention in order to prevent minimal displacement of tuberosity or articular surface from compromising the long term articular function. The objective was to assess the functional outcome of patients treated with PHILOS (the proximal humeral internal locking osteosynthesis) plate in proximal humerus fracture.</p><p class="abstract"><strong>Methods:</strong> 42 patients age group range between 20 and 80 years 61.9% are male and 38.1% are female treated with philos plate. Functional outcome measured by using Constant and Murley score.<strong></strong></p><p class="abstract"><strong>Results:</strong> 50% were Neer two part fractures, 35.7%, three part fractures, 14.3%, four part fractures. After 6 month follow up functional outcome assessed by using constant and Murley score. Excellent outcome in 1 (2.4%) good outcome in 13 (31%), fair outcome in 19 (45.2%) and poor outcome in 9 (21.4%) noted.</p><p class="abstract"><strong>Conclusions:</strong> PHILOS plate fixation of proximal humerus fracture is an effective surgical technique in maintaining stability of fractures and there is significant improvement in functional outcome.</p>

Coverage of Severely Burn Injured Knee with Supercharged Reverse ALT Flap: Avoiding Limb Amputation

Primary skin and soft tissue reconstruction of large defects around the knee may be a challenge for the plastic surgeon. Fasciocutaneous flaps play an essential role in achieving functional and aesthetic restoration. We present the surgical reconstruction of an extensive 3rd degree burn injury with knee joint capsule and ligaments involvement in a 51-year-old patient. Devitalized structures were firstly debrided and a supercharged reverse anterolateral thigh (RALT) flap was used to cover the resultant tissue defect. The ALT fascia was employed to reconstruct the damaged joint capsule in order to restore articular function. The supercharged RALT flap has a greater blood supply compared with standard flaps and enables us to use larger flaps to reconstruct extensive knee and proximal leg tissue defects.

The Use of Cadaveric Meniscus for Joint Resurfacing of the Wrist and Hand

HYPOTHESIS: Osteochondral defects of the carpometacarpal (CMC), metacarpophalangeal (MCP), and proximal interphalangeal (PIP) joints often necessitate joint arthrodesis or mechanical arthroplasty. Cadaveric meniscus has long been used for large joint resurfacing,1,2 but its application to smaller joints of the hand is less well understood. In severely arthritic thumb and finger joints, we propose the use of cadaveric meniscus for joint resurfacing as an off-the-shelf alternative to address osteochondral defects and restore articular function. METHODS: Thirty-six patients with osteoarthritis of the CMC, MCP, or PIP joints underwent joint resurfacing with cadaveric meniscus. Patient demographics and operative information were recorded. Postoperative Disability of the Shoulder, Arm and Hand scores, Wong-Baker pain scale score, grip strength, and pinch strength were compared to preoperative scores at 6 weeks and 6 months. RESULTS: Twenty-one females and 15 males, with mean age of 56.7 years (42–73), underwent a total 43 joint reconstructions. Reconstructive sites included thumb carpometacarpal joint (n = 21), thumb metacarpal joint (n = 2), thumb interphalangeal joint (n = 2), digit metacarpal joint (n = 3), and digit proximal interphalangeal joint (n = 2). Mean Disability of the Shoulder, Arm and Hand score decreased from an average of 39.2 (16–91) to 22.7 (3–55) at 6 months and pain scale scores decreased from an average of 6.5 (4–10) to 1.6 (0–4). Grip strength increased from 38.7 (3–84) to 44.5 (8–94) and pinch increased from 10.3 (1–19) to 10.7 (2–20). There were no complications related to the meniscus, and no patients required revision surgery. CONCLUSION: In this series of 42 joint reconstructions, we demonstrate the successful use of cadaver meniscus in hand joint arthroplasty to reduce subjective pain and disability scores, as well as to improve objective strength measures, including grip and pinch strength. Our early results suggest that cadaveric meniscus for small joint arthroplasty represents a viable joint salvage option or adjunct to preserve pain-free motion and avoid total joint arthrodesis. REFERENCES: 1. Rosso F, Bisicchia S, Bonasia DE, et al. Meniscal allograft transplantation: a systematic review. Am J Sports Med. 2015;43:998–1007. 2. Kang RW, Lattermann C, Cole BJ. Allograft meniscus transplantation: background, indications, techniques, and outcomes. J Knee Surg. 2006;19:220–230.

A serial multiparametric quantitative magnetic resonance imaging study to assess proteoglycan depletion of human articular cartilage and its effects on functionality

Water, collagen, and proteoglycans determine articular cartilage functionality. If altered, susceptibility to premature degeneration is increased. This study investigated the effects of enzymatic proteoglycan depletion on cartilage functionality as assessed by advanced Magnetic Resonance Imaging (MRI) techniques under standardized loading. Lateral femoral condylar cartilage-bone samples from patients undergoing knee replacement (n = 29) were serially imaged by Proton Density-weighted and T1, T1ρ, T2, and T2* mapping sequences on a clinical 3.0 T MRI scanner (Achieva, Philips). Using pressure-controlled indentation loading, samples were imaged unloaded and quasi-statically loaded to 15.1 N and 28.6 N, and both before and after exposure to low-concentrated (LT, 0.1 mg/mL, n = 10) or high-concentrated trypsin (HT, 1.0 mg/mL, n = 10). Controls were not treated (n = 9). Responses to loading were assessed for the entire sample and regionally, i.e. sub- and peri-pistonally, and zonally, i.e. upper and lower sample halves. Trypsin effects were quantified as relative changes (Δ), analysed using appropriate statistical tests, and referenced histologically. Histological proteoglycan depletion was reflected by significant sub-pistonal decreases in T1 (p = 0.003) and T2 (p = 0.008) after HT exposure. Loading-induced changes in T1ρ and T2* were not related. In conclusion, proteoglycan depletion alters cartilage functionality and may be assessed using serial T1 and T2 mapping under loading.

In vivo cartilage regeneration in a multi-layered articular cartilage architecture mimicking scaffold.

AimsExtracellular matrix (ECM) and its architecture have a vital role in articular cartilage (AC) structure and function. We hypothesized that a multi-layered chitosan-gelatin (CG) scaffold that resembles ECM, as well as native collagen architecture of AC, will achieve superior chondrogenesis and AC regeneration. We also compared its in vitro and in vivo outcomes with randomly aligned CG scaffold.MethodsRabbit bone marrow mesenchymal stem cells (MSCs) were differentiated into the chondrogenic lineage on scaffolds. Quality of in vitro regenerated cartilage was assessed by cell viability, growth, matrix synthesis, and differentiation. Bilateral osteochondral defects were created in 15 four-month-old male New Zealand white rabbits and segregated into three treatment groups with five in each. The groups were: 1) untreated and allogeneic chondrocytes; 2) multi-layered scaffold with and without cells; and 3) randomly aligned scaffold with and without cells. After four months of follow-up, the outcome was assessed using histology and immunostaining.ResultsIn vitro testing showed that the secreted ECM oriented itself along the fibre in multi-layered scaffolds. Both types of CG scaffolds supported cell viability, growth, and matrix synthesis. In vitro chondrogenesis on scaffold showed an around 400-fold increase in collagen type 2 (COL2A1) expression in both CG scaffolds, but the total glycosaminoglycan (GAG)/DNA deposition was 1.39-fold higher in the multi-layered scaffold than the randomly aligned scaffold. In vivo cartilage formation occurred in both multi-layered and randomly aligned scaffolds treated with and without cells, and was shown to be of hyaline phenotype on immunostaining. The defects treated with multi-layered + cells, however, showed significantly thicker cartilage formation than the randomly aligned scaffold.ConclusionWe demonstrated that MSCs loaded CG scaffold with multi-layered zonal architecture promoted superior hyaline AC regeneration.Cite this article: Bone Joint Res 2020;9(9):601–612.

Interpositional Arthroplasty Using Mammary Capsule for Finger Joints: A Novel Technique.

Degenerative osteoarthritis frequently affects the hands, altering the movements; surgical therapy includes arthrodesis and arthroplasty. We report the case of a female patient who presented arthrosis in the hands, severe on the proximal interphalangeal (PIP) joints, initially in her right index finger, and subsequently in the index and middle left fingers. At first, she received treatment in the PIP joint of the right index finger with a silicone implant; later on, she presented fracture of it and required replacement 8 years later. In the PIP joints of index and middle left fingers, treatment was made with interposition arthroplasty by mammary implant capsule. We present the postoperative progression of the silicone versus mammary capsule interposition arthroplasty. It is remarkable that, over time, articular function of the intervened joints with capsular arthroplasty remained stable with good motion, while range of motion in other fingers was reduced as a consequence of osteoarthritis. The frequency of patients presenting simultaneously with mammary capsule contracture and osteoarthritis is low, but this novel technique is nonetheless worthwhile to take into consideration.

Irisin Recovers Osteoarthritic Chondrocytes In Vitro.

Physical exercise favors weight loss and ameliorates articular pain and function in patients suffering from osteoarthritis. Irisin, a myokine released upon muscle contraction, has demonstrated to yield anabolic effects on different cell types. This study aimed to investigate the effect of irisin on human osteoarthritic chondrocytes (hOAC) in vitro. Our hypothesis was that irisin would improve hOAC metabolism and proliferation. Cells were cultured in growing media and then exposed to either phosphate-buffered saline (control group) or human recombinant irisin (experimental group). Cell proliferation, glycosaminoglycan content, type II/X collagen gene expression and protein quantification as well as p38/extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK), protein kinase B (Akt), c-Jun N-terminal kinase (JNK), and nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) involvement were evaluated. Furthermore, gene expression of interleukin (IL)-1 and -6, matrix metalloproteinase (MMP)-1 and -13, inducible nitric oxide synthase (iNOS), and tissue inhibitor of matrix metalloproteinases (TIMP)-1 and -3 were investigated following irisin exposure. Irisin increased hOAC cell content and both type II collagen gene expression and protein levels, while decreased type X collagen gene expression and protein levels. Moreover, irisin decreased IL-1, IL-6, MMP-1, MMP-13 and iNOS gene expression, while increased TIMP-1 and TIMP-3 levels. These effects seemed to be mediated by inhibition of p38, Akt, JNK and NFκB signaling pathways. The present study suggested that irisin may stimulate hOAC proliferation and anabolism inhibiting catabolism through p38, Akt, JNK, and NFκB inactivation in vitro, demonstrating the existence of a cross-talk between muscle and cartilage.

Promoted Viability and Differentiated Phenotype of Cultured Chondrocytes With Low Level Laser Irradiation Potentiate Efficacious Cells for Therapeutics.

Effective clinical treatments of cartilage lesions in affected joints require large numbers of viable chondrogenic cells generated through in vivo stimulation or ex vivo expansion of chondrocytes isolated from small biopsy specimens. Conventional passaging of chondrocytes in culture provides sufficient cells for treatments but these cells usually lose their differentiated phenotype. This leads to the formation of fibrocartilaginous tissue due to a malfunctioning repair process. Biostimulation of passaging chondrocytes with low level laser irradiation (LLLI) may theoretically produce more functional chondrocytes for cell-based repair of cartilage defects. Molecular and cellular analyses, cytochemistry, cell cultivation, and microscopy showed that LLLI treatments were found to (1) increase chondrocyte viability, (2) promote secretion of matrix proteins, (3) upregulate expression of chondrogenic genes, and (4) downregulate gene expression of cell destructive proteases and genes coding for mediators involved in the extrinsic apoptosis signaling pathway. Furthermore, LLLI attenuated induction of genes associated with cell death and matrix breakdown induced by IL-1β, some of which was seen at the protein level, with verification of effects on gene expression in the C28/I2 human chondrocyte line. LLLI treatments during culture generated larger numbers of viable chondrocytes compared to untreated cultures. Moreover, LLLI-treated chondrocytes in culture also rectified and simultaneously maintained their differentiated phenotype. Cultured chondrocytes treated with LLLI are a promising cell source for repairing cartilage lesions in vivo and restoration of articular function using tissue engineering strategies.

Properties of Cartilage-Subchondral Bone Junctions: A Narrative Review with Specific Focus on the Growth Plate.

The purpose of this narrative review is to summarize what is currently known about the structural, chemical, and mechanical properties of cartilage-bone interfaces, which provide tissue integrity across a bimaterial interface of 2 very different structural materials. Maintaining these mechanical interfaces is a key factor for normal bone growth and articular cartilage function and maintenance. A comprehensive search was conducted using Google Scholar and PubMed/Medline with a specific focus on the growth plate cartilage-subchondral bone interface. All original articles, reviews in journals, and book chapters were considered. Following a review of the overall structural and functional characteristics of the physis, the literature on histological studies of both articular and growth plate chondro-osseous junctions is briefly reviewed. Next the literature on biochemical properties of these interfaces is reviewed, specifically the literature on elemental analyses across the cartilage-subchondral bone junctions. The literature on biomechanical studies of these junctions at the articular and physeal interfaces is also reviewed and compared. Unlike the interface between articular cartilage and bone, growth plate cartilage has 2 chondro-osseous junctions. The reserve zone of the mature growth plate is intimately connected to a plate of subchondral bone on the epiphyseal side. This interface resembles that between the subchondral bone and articular cartilage, although much less is known about its makeup and formation. There is a notably paucity of information available on the structural and mechanical properties of reserve zone-subchondral epiphyseal bone interface. This review reveals that further studies are needed on the microstructural and mechanical properties of chondro-osseous junction with the reserve zone.

The Influence of Hand Dominance on the Degree of Deformities in Patients With Systemic Lupus Erythematosus and Jaccoud Arthropathy.

Joint deformities in Jaccoud arthropathy (JA), associated with systemic lupus erythematosus (SLE), can lead to a reduction in articular function and an impaired quality of life. There is controversy in the literature as to whether hand dominance contributes to deformities observed in rheumatoid arthritis and other forms of rheumatism. The purpose of this study was to assess whether hand dominance has any influence on the degree of deformity or joint range of motion in patients with JA associated with SLE. This was a pilot cross-sectional study of 22 female patients (mean age, 46.18 ± 12.61 years) with both SLE and JA. Each patient's hand grip and hand and wrist joint range of motion were assessed by the same examiner. The Wilcoxon test was used to compare the median values of the angles and muscular strength found between the sides. All the study participants were right-side dominant. The median muscle strength of the right and left hands was 13.25 kilogram-force (KgF) (range, 7.00-18.00 KgF) and 10.50 KgF (range, 7.50-17.25 KgF), respectively. Both the fingers of the right and left hands had a median ulnar drift of 10.00°; however, their ranges differed (right, 4.50° to 20.00°; left: 0.00° to 15.50°). No statistically significant differences were found in the extension angulation of the proximal interphalangeal joints or the flexion of the distal interphalangeal joints of the second to fifth fingers, between the dominant and nondominant hands. Hand dominance does not seem to influence the degree of JA deformities in patients with SLE.

An Evidence-based Review of Medicinal Plants used in Traditional Persian Medicine for Treatment of Osteoarthritis.

Osteoarthritis (OA) is known to be the leading cause of pain and disability in the elderly. The prevalence of this disease in adults over 60 years was 9.6% in men and 18% in women. The therapeutic goals of this disease generally include pain relief with the least side effects, improvement of articular function and improvement of life, in which pharmacological and nonpharmacological treatments are performed in different protocols. Due to the common side effects of pain relievers and complaints after invasive joint surgeries, there is a growing interest in the use of Traditional and Complementary protocols in OA treatment. In this paper, different sources of Traditional Persian Medicine (TPM) were searched to obtain any evidence evaluating any medicinal plants in the management of OA. Over 250 effective medicinal plants for the treatment of OA have been introduced in these sources, and by searching electronic databases including PubMed and Scopus, we have found that of these plants, 39 have direct or indirect evidence in the treatment of this complication by different mechanism of actions such as effect on Body mass index (BMI), obesity and dyslipidemia, anti-inflammatory, anti-nociceptive and antioxidant activity. The most important medicinal plants with direct evidence in the management of OA are Allium sativum, Commiphora mukul, Linum usitatissimum, Matricaria chamomilla, Nigella sativa, Zingiber officinale, and Piper nigrum. Medicinal plants seem to be a valuable source for discovering and identifying new drugs for treatment of OA; however, since most of the studies are preclinical, further clinical trials are required to achieve more conclusive results.

Therapeutic exercise and radiofrequency in the rehabilitation project for hip osteoarthritis pain.

Severe hip osteoarthritis is responsible for disabling pain and functional impairment of the joint. Although total hip arthroplasty (THA) is a successful treatment, some patients have multiple comorbidities that represent contraindications for THA. Conventional drug therapies are often ineffective or responsible for numerous side effects. For these patients, it is difficult to draw up an acceptable rehabilitation path, as the main limitation is intense pain. New rehabilitation strategies that relieve pain and improve articular function need to be developed. The combination of traditional treatments such as education and therapeutic exercise with innovative, minimally-invasive therapies such as continuous radiofrequency (CRF) appears to reduce hip pain by determining the neurolysis of the joint. The aim of our study was to describe the reduction in pain and improvements in joint function when CRF is combined with the therapeutic exercise in rehabilitation of patients with severe hip osteoarthritis. Case series study. Rehabilitation service outpatients. Twenty-five patients with severe hip osteoarthritis causing disabling pain and with contraindications to THA, and for whom conventional drug therapies were ineffective or responsible for numerous side effects. The study design included: initial clinical-functional assessment using the Harris Hip Score (HHS), the Numeric Rating Scale (NRS) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC); a pre-lesion anaesthetic block; hip neuroablation with CRF; a three-week kinesitherapy protocol (3 sessions per week); two further assessments using the same scales one month (T1) and six months (T2) after CRF. Improvements at T1 and T2 follow-ups, after CRF (P=0.000) were recorded for articular pain and function. However, results at T2 were worse than those at T1 (P=0.000). CRF combined with therapeutic exercise in rehabilitation of severe hip osteoarthritis is an attractive option for significant pain relief as it allows patients to carry out kinesitherapy more easily. CRF could represent a valid alternative in the rehabilitation of patients with severe hip osteoarthritis especially when other therapeutic approaches are unworkable.

A coordinate-system-independent method for comparing joint rotational mobilities.

Three-dimensional studies of range of motion currently plot joint poses in a 'Euler space' whose axes are angles measured in the joint's three rotational degrees of freedom. Researchers then compute the volume of a pose cloud to measure rotational mobility. However, pairs of poses that are equally different from one another in orientation are not always plotted equally far apart in Euler space. This distortion causes a single joint's mobility to change when measured based on different joint coordinate systems and precludes fair comparison among joints. Here, we present two alternative spaces inspired by a 16th century map projection - cosine-corrected and sine-corrected Euler spaces - that allow coordinate-system-independent comparison of joint rotational mobility. When tested with data from a bird hip joint, cosine-corrected Euler space demonstrated a 10-fold reduction in variation among mobilities measured from three joint coordinate systems. This new quantitative framework enables previously intractable, comparative studies of articular function.

Imaging of Failed Cartilage Repair

Abstract Osteoarthritis is an extremely common cause of morbidity throughout the world. Current standard of care treatment strategies focus on repairing or replacing articular cartilage defects, as methods of regenerating articular cartilage are still largely in experimental stages. Cartilage repair techniques, typically used in the setting of focal defects, allow replacement of focally damaged cartilage utilizing either donor tissue or the patient's own tissue, with the goal of restoring normal articular surface function, preventing further joint damage, and improving clinical symptoms. While these procedures succeed in many, as with any intervention, outcomes are not universally successful. Imaging can be useful in evaluation of patients following cartilage repair, providing assessment of technical success, evolution of graft tissue over time, and potential complications. Magnetic resonance imaging, in particular, allows comprehensive imaging evaluation of repair tissue, as well as potential alternate causes of clinical symptoms. Familiarity with the expected imaging appearance of cartilage repair, and particularly the expected evolution over time, is crucial for the accurate interpretation of imaging following cartilage repair.

Sida tuberculata reduces oxidative stress and pain caused by the knee osteoarthritis.

Knee osteoarthritis (OA) cause pain and edema, as well as unbalance between the production of reactive oxygen species and antioxidant activity. These problems interfere with the articular function, leading to a significant loss of life quality. Sida tuberculata R.E.Fr. is an herbaceous plant belonging to the Malvaceae family found in southern Brazil. This plant has traditionally been consumed as an aqueous extract and popularly used in the treatment of many diseases, with antioxidant and antimicrobial activity, reducing pain and inflammation. To verify the effects of S. tuberculata extract obtained from leaves on oxidative, toxic and nociceptive parameters induced by knee OA in rats. Aqueous extracts of S. tuberculata were evaluated under phytochemical analyses. Knee Osteoarthritis was induced in rats with monosodium iodoacetate (1.5 mg/50 μl) and treated with S. tuberculata extract. The animals were treated orally with 3 doses of S. tuberculata extract (STE): 1.5, 5 and 15 mg/ml, for 14 days. For biochemical analyses, the following tests were performed: lipid peroxidation, carbonylated protein content, superoxide dismutase activity, non-protein thiol levels and myeloperoxidase activity. For the evaluation of pain and edema we verify mechanical and thermal hyperalgesia, spontaneous pain observation and measurement of knee edema with a caliper. For histological evaluations, the animal knee joints were removed. For toxicity evaluation, the levels of aspartate aminotransferase, alanine aminotransferase and urea, as well as the relative weight of the organs were analyzed. The S. tuberculata phytochemical analyses showed the majority peak corresponding to 20-hydroxyecdysone (20HE). The plant extract decreased damages related to oxidative stress in the blood serum (lipid peroxidation and carbonyl content) Overall, the STE 5 mg Group presented the greater statistical significance, in the blood serum samples, in relation to the other groups, being the most relevant result. The S. tuberculata groups presented pain decrease, lower neutrophil activity in the knee, and increased blood serum activity. The animals of S. tuberculata groups showed a decrease in mechanical hyperalgesia. The animals treated also presented lower scores for spontaneous pain. It was observed that the dose of 5 mg presented, once again, more expressive results, since the animals of this group had a higher frequency (greater number of days) with significant decrease of pain. In the histological analysis, in the STE 5 mg group, the articular cartilage lesions were observed at an intermediate point between the damage found in the MIA and Diclofenac groups. Besides that, the STE did not show significant changes in oxidative stress damage in liver and kidney samples. Blood serum samples did not indicate significant differences in liver and renal function. As well as, there were no differences in mean relative body weights in relation to control groups (Salina and MIA). S. tuberculata reduced the damage due to oxidative stress and pain caused by knee osteoarthritis in rats. In addition, the extract presented no toxicity. Our results suggest that S. tuberculata seems to have a therapeutic potential in the osteoarthritis treatment.

Protective effect of vildagliptin on TNF-α-induced chondrocyte senescence.

Osteoarthritis (OA) is a common age-related disorder. Chondrocytes in joint tissue play a critical role in normal articular cartilage function and tissue homeostasis. Local inflammatory cytokine-induced chondrocyte senescence contributes to the development and progression of OA. Various dipeptidyl peptidase-4 (DPP-4) inhibitors have been widely used to treat type 2 diabetes. Here, we report a novel pharmacological role of the DPP-4 inhibitor vildagliptin in chondrocyte senescence. Our data indicate that DPP-4 is an inducible factor responsive to tumor necrosis factor-α (TNF-α) treatment in chondrocytes. The inhibition of DPP-4 by vildagliptin ameliorates TNF-α-induced chondrocyte senescence as determined by cellular senescence-associated β-galactosidase (SA-β-Gal) activity. Vildagliptin displayed protective capabilities against TNF-α-induced chondrocyte cell cycle arrest in the G1 phase. Moreover, vildagliptin suppresses the three major TNF-α-induced chondrocyte senescence proteins including p53, p21, and plasminogen activator inhibitor-1 (PAI-1). Vildagliptin also suppresses TNF-α-induced p53 acetylation at K382. Consistently, our findings demonstrate the inhibitory effect of vildagliptin on p53 acetylation, which is mediated by sirtuin 1 (SIRT1) as the inhibition of SIRT1 negated the inhibitory action of vildagliptin on p53 acetylation. Furthermore, we found that the effect of vildagliptin on SIRT1 protection is adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) dependent, and the inhibition of AMPK activity negated the protection of vildagliptin against SIRT1 and chondrocytes senescence. In conclusion, our study explored the molecular mechanism and protective effect of the antidiabetic drug vildagliptin against chondrocyte senescence, and our findings imply that vildagliptin has a therapeutic potential in OA. © 2019 IUBMB Life, 1-2, 2019.

Detection of Early-Stage Degeneration in Human Articular Cartilage by Multiparametric MR Imaging Mapping of Tissue Functionality

To assess human articular cartilage tissue functionality by serial multiparametric quantitative MRI (qMRI) mapping as a function of histological degeneration. Forty-nine cartilage samples obtained during total knee replacement surgeries were placed in a standardized artificial knee joint within an MRI-compatible compressive loading device and imaged in situ and at three loading positions, i.e. unloaded, at 2.5 mm displacement (20% body weight [BW]) and at 5 mm displacement (110% BW). Using a clinical 3.0 T MRI system (Achieva, Philips), serial T1, T1ρ, T2 and T2* maps were generated for each sample and loading position. Histology (Mankin scoring) and biomechanics (Young’s modulus) served as references. Samples were dichotomized as intact (int, n = 27) or early degenerative (deg, n = 22) based on histology and analyzed using repeated-measures ANOVA and unpaired Student’s t-tests after log-transformation. For T1ρ, T2 and T2*, significant loading-induced differences were found in deg (in contrast to int) samples, while for T1 significant decreases in all zones were observed, irrespective of degeneration. In conclusion, cartilage functionality may be visualized using serial qMRI parameter mapping and the response-to-loading patterns are associated with histological degeneration. Hence, loading-induced changes in qMRI parameter maps provide promising surrogate parameters of tissue functionality and status in health and disease.

Patient-reported health outcomes for severe knee osteoarthritis after conservative treatment with an intra-articular cell-free formulation for articular cartilage regeneration combined with usual medical care vs. usual medical care alone: A randomized controlled trial.

Osteoarthritis (OA) is a major public health problem characterized by joint pain, fatigue, functional limitation and decreased quality of life of the patient, which results in increased use of healthcare services and high economical costs. A promising novel bioactive cell-free formulation (BIOF2) for cartilage regeneration has recently been tested in pre-clinical and clinical trials, and has demonstrated a success rate similar to that of total joint arthroplasty for the treatment of severe knee OA. The present study evaluated the efficacy of treatment with BIOF2, by including it within a conservative regimen of ‘usual medical care’ of knee OA, and whether its efficacy was affected in subgroups of patients presenting with comorbidities that exacerbate OA. A prospective, randomized, 2-arm parallel group phase III clinical trial was conducted, which included 105 patients in the ‘usual medical care’ group (paracetamol/NSAIDs and general care provided by the family physician) and 107 patients in the BIOF2 group (usual medical care + intra-articular BIOF2 application at 0, 1 and 2 months). Two aspects were evaluated at 0, 6 and 12 months: i) Minimal clinically important improvement (MCII), based on 30% improvement of pain from the baseline; and ii) the Patient Acceptable Symptom State (PASS), a questionnaire that determines patient well-being thresholds for articular pain and function. Adverse effects and regular NSAID use were registered. At 12 months, BIOF-2 treatment produced MCII in 70% of the patients and >50% achieved PASS. Excluding the patients with class 2 obesity or malalignment conditions (genu varum or genu valgum >20 degrees), the experimental treatment produced MCII and PASS in 100 and 92% of patients, respectively, compared with 25 and 8% in the group of usual medical care (P<0.001). No patient with malalignment and treatment with BIOF2 achieved PASS. Notably, there were no serious adverse effects. To conclude, BIOF2 is a safe therapeutic alternative that is easy to implement together with usual medical care for knee OA. Trial registration: Cuban Public Registry of Clinical Trials (RPCEC) Database RPCEC00000277. Retrospectively registered June, 2018.

Condylar dysfunctional remodeling and recortication: a case-control study.

Temporo-mandibular disorders (TMD) is a collective term comprehending different clinical issues involving masticatory muscles, temporo-mandibular joint (TMJ) and other associated structures. TMD diagnosis is not made for its pathogenesis or etiology, but mainly on clinical symptoms. Primary dysfunction develops mostly on four factors: individual predisposition, high psychomotor activity (due to stress or parafunction), occlusal instability and low or absent tissue adaptation capability. On the other hand, secondary disorders can be caused by hereditary or congenital diseases, rheumatic inflammatory diseases, autoimmune and tumoral diseases. During their function, the condyles undergo a structural adaptive and physiological remodeling, but when mechanical stress exceeds adaptive capability, dysfunctional remodeling phenomena may occur. It is characterized by significant condylar morphological modifications at the level of the head of the condyle (smaller condyle), break of cortical integrity and reduced mandibular ramus height with subsequent mandibular retrusion and articular function alteration. The aim of this study is to compare condylar recortication amount, and pain reduction after two different therapeutic protocols. This is a case-control study. Twenty TMD patients were chosen and each of them underwent a documentation protocol including extraoral and intraoral photographs, dental casts, casts mounting on the articulator to evaluate CPI (CO-CR discrepancy index) and cone beam computed tomography (CBCT) of the mandibular condyles taken in closed mouth position. For the radiographic evaluation, a Planmeca ProMax 3D Mid system was utilized with an acquiring volume of 80×80 mm dimension, exposition 90 kV, 10.0 mA, 12 seconds with a DAP (Dose Area Product) of 1094 mGy·cm2 for each condyle. The acquired volume was elaborated by the Planmeca Romexis software v. 3.2.0.R and TMJ module. Seven coronal cuts and 10 sagittal cuts were performed on the head of the condyle to highlight the amount of cortication, before and after the application of two different therapeutic protocols. Protocol number 1 (N.=10 patients) included the exclusive use of a splint, while protocol number 2 (N.=10 patients) included the use of a splint associated with pharmacological therapy (NSAIDs, antioxidant, omega 3). The revaluation was performed on asymptomatic patient after a period of 6-8 months. The pain for each patient was assessed by a Visual Analogue Scale (VAS) from 0 to 10, 0 meaning no pain and 10 the worst pain ever felt. The VAS was evaluated after 10 days from the beginning of the treatment, after 3 months and after 8 months at the end of the treatment. Statistical analyses were carried using a χ2 test (P value <0.05). No significant differences in the amount of cortication were found in the radiographic revaluation between the two different therapeutic protocols, even though it was noticed that the use of medicaments brought to a resolution of the symptoms in a shorter period of time (P=0.00001 after 10 days; P=0.0251 after 3 months). According to this study, pharmacological protocol in the therapy of TMD does not seem to affect condylar cortication. Medicaments although seem to accelerate the disappearance of clinic symptomatology, but more researches are needed to valid these findings.