Osteophyte Growth Research Articles

A new approach to the treatment of spinal instability: Fusion or structural reinforcement without surgery?

Spinal instability related low back pain is a common condition resulting from degeneration and loss of stiffness of the intervertebral joint. In order to restore stability, highly invasive surgical fusion is needed for patients who are not responding to conservative treatment. Given the risk and complications of surgery, there has been the urge for improvement with a less invasive solution. Formation of vertebral body osteophytes is a common observation that has been treated as a degenerative condition. However, recent studies have associated it with reduced motion of spinal segments. Unlike the traditional view, we regard it as adaptive reactions aiming to repair and hypothesize that the spinal segments could be stabilized or fused by intentionally induced osteophytes growth at the mobile parts of the intervertebral joint. This could be achieved by injecting Bone Morphogenetic Proteins to the anterior ends of the vertebral bodies and/or the facet joints on both sides of two consecutive vertebrae percutaneously. If verified, it would be the first time that fusion could be achieved without surgery. Hence it would provide a valuable alternative to current treatments of spinal instability. Preliminary test in favor of this hypothesis is presented and we recommend that a formal study with sufficient number of samples is needed for verification.

Osteophyte volume calculation using dissimilarity-excluding Procrustes registration of archived bone models from healthy volunteers.

Osteophytes are associated with later stage osteoarthritis and are most commonly described using semiquantitative radiographic grading systems. A detailed understanding of osteophyte formation is, in part, limited by the ability to quantify bone pathology. Osteophytes can be quantified relative to pre-osteoarthritic bone, or to the contralateral bone if it is healthy; however, in many cases, neither are available as references. We present a method for computing three-dimensional (3D) osteophyte models using a library of healthy control bones. An existing data set containing the computed tomography scans of 90 patients with first carpometacarpal osteoarthritis (OA) and 46 healthy subjects were utilized. A healthy bone that best fit each OA subject's bone was determined using a dissimilarity-excluding Procrustes registration technique (DEP) that minimized the influence of dissimilar features (ie, osteophytes). The osteophyte model was then computed through Boolean subtraction of the reference bone model from the OA bone model. DEP reference bones conformed significantly better to the OA bones (P < .0001) than by finite difference iterative closest point registration (root mean squared distances, 0.33 ± 0.05 and 0.41 ± 0.16 mm, respectively). The effect of library size on dissimilarity measure was investigated by leave-k-out cross-validation randomly reducing k from 46 to 1. A library of n ≥ 31 resulted in less than 10% difference from the theoretical minimum value. The proposed method enables quantification of osteophytes when the disease-free bone or the healthy contralateral bone is not available for any 3D data set. Quantifying osteophyte formation and growth may aid in understating the associated mechanisms in OA.

Experimental Study of Anti-Interventional Endothelial Progenitor Cells Combined with Mesenchymal Stem Cells in Large Femoral Defects

Mesenchymal stem cells (MSCs) and vascular endothelial progenitor cells (EPCs) have the potential for self-renewal and multi-directional differentiation. Their combination therapy is beneficial for treating orthopedic diseases. However, the role of antibiotic-interventional EPCs combined with MSCs in large femoral defects remains unclear. Rabbit MSCs and EPCs were isolated and EPCs were cultured in the presence of 1% green chain double antibody. The femoral segmental bone defect model was prepared and randomly divided into control group, MSCs group, EPCs group, EPCs + MSCs group, and autologous oxygen release nano-bionic scaffolds were combined with MSCs, EPCs, EPCs + MSCs followed by analysis of osteophytes by HE staining, bone density, ALP activity, TGF-β1 secretion by ELISA, and level of VEGF, Runx2 and OC by Real time PCR. MSCs, EPCs and combined treatment for large femoral bone defects can significantly improve osteophyte growth, promote bone density, increase ALP activity and TGF-β1 secretion, as well as increase VEGF, Runx2 and OC expression. Compared with control group, there was a significant difference (P &lt; 0.05) with combined treatment group having more significant effect on bone repair. Antibioticintervention of EPCs combined with MSCs promotes osteogenic activity and bone repair ability in large femoral defects.

Experimental Study on Construction of Tissue Engineered Bone by Autologous Oxygen Release Nano-Bionic Scaffold Combined with Bone Morphogenetic Protein-2 Induced Bone Marrow Mesenchymal Stem Cells

Bone marrow mesenchymal stem cells (BMSCs) are used for bone tissue engineering. BMP-2 and autologous oxygen-releasing nano-bionic scaffolds promote bone differentiation of BMSCs. Our study intends to evaluate the role of autologous oxygen-releasing nano-bionic scaffolds combined with BMP-2-induced BMSCs in the construction of tissue engineered bone. Rat BMSCs were isolated and transfected with NC (negative control group) and BMP-2 (BMP-2 plasmid group), respectively. Healthy male SD rats were randomly and equally divided into fracture group, negative control group and the BMP-2 group which was implanted with autologous oxygen-releasing nano-bionic scaffolds to synthesize BMSCs and transfected with BMP-2 plasmids respectively followed by analysis of osteophytes growth, ALP activity, expression of BMP-2, type II collagen, Runx2 and OC by real time PCR, TGF-β1 secretion by ELISA and BMP-2 protein expression by western blot. BMSCs induced by autologous oxygen release nano-bionic scaffold combined with BMP-2 can significantly promote the increase of bone mineral density, increase the expression of Runx2 and OC, promote ALP activity, upregulate type II collagen, BMP-2 mRNA and protein, and TGF-β1 secretion compared to fracture group (P &lt; 0.05). The BMSCs induced by autologous oxygen-releasing nanobionic scaffolds transfected with BMP-2 had a more significant effect on bone repair. Autologous oxygen-releasing nano-bionic scaffolds combined with BMP-2-induced BMSCs can promote bone healing by regulating BMP-2 and increasing osteogenesis at the bone defect.

18F]‐Sodium Fluoride PET/MR Imaging for Bone–Cartilage Interactions in Hip Osteoarthritis: A Feasibility Study

ABSTRACTThis study characterized the distribution of [18F]‐sodium fluoride (NaF) uptake and blood flow in the femur and acetabulum in hip osteoarthritis (OA) patients to find associations between bone remodeling and cartilage composition in the presence of morphological abnormalities using simultaneous positron emission tomography and magnetic resonance imaging (PET/MR), quantitative magnetic resonance imaging (MRI) and femur shape modeling. Ten patients underwent a [18F]‐NaF PET/MR dynamic scan of the hip simultaneously with: (i) fast spin‐echo CUBE for morphology grading and (ii) T 1ρ/T 2 magnetization‐prepared angle‐modulated partitioned k‐space spoiled gradient echo snapshots for cartilage, bone segmentation, bone shape modeling, and T 1ρ/T 2 quantification. The standardized uptake values (SUVs) and Patlak kinetic parameter (K pat) were calculated for each patient as PET outcomes, using an automated post‐processing pipeline. Shape modeling was performed to extract the variations in bone shapes in the patients. Pearson's correlation coefficients were used to study the associations between bone shapes, PET outcomes, and patient reported pain. Direct associations between quantitative MR and PET evidence of bone remodeling were established in the acetabulum and femur. Associations of shaft thickness with SUV in the femur (p = 0.07) and K pat in the acetabulum (p = 0.02), cam deformity with acetabular score (p = 0.09), osteophytic growth on the femur head with K pat (p = 0.01) were observed. Pain had increased correlations with SUV in the acetabulum (p = 0.14) and femur (p = 0.09) when shaft thickness was accounted for. This study demonstrated the ability of [18F]‐NaF PET‐MRI, 3D shape modeling, and quantitative MRI to investigate cartilage‐bone interactions and bone shape features in hip OA, providing potential investigative tools to diagnose OA. © 2019 The Authors. Journal of Orthopaedic Research ® published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society J Orthop Res 37:2671–2680, 2019

Osteophyte growth in early thumb carpometacarpal osteoarthritis

Osteophyte formation is a critical part of the degeneration of a joint with osteoarthritis (OA). While often qualitatively described, few studies have succeeded in quantifying osteophyte growth over time. Using computed tomography (CT) image data from a longitudinal, observational study of thumb carpometacarpal (CMC) OA, our aim was to quantify osteophyte growth volume and location over a three-year period in men and women. Ninety patients with early thumb OA were recruited and assessed at baseline, 1.5 years, and 3 years with CT imaging. Osteophyte volume and location on the trapezium and first metacarpal were determined using a library of 46 healthy subjects as a nonarthritic reference database. There was a significant increase in osteophyte volume for women and men over the three-year follow-up in the trapezium (86.8mm3-120.5mm3 and 165.1mm3-235.3mm3, means respectively) and in the proximal metacarpal (63mm3-80.4mm3, and 115.8mm3-161.7mm3, respectively). The location of osteophyte initiation and growth was consistent across subjects and was located in non-opposing regions on the trapezium and first metacarpal. Osteophyte growth occurred about the radial and ulnar margins of the trapezial facet, while on the proximal metacarpal, growth occurred principally about the volar and dorsal margins of the facet. Osteophyte growth occurred in early thumb osteoarthritis over three years. Growth was localized in specific, non-opposing regions on the trapezium and metacarpal, raising intriguing questions about the triggers for their formation, whether the mechanisms are mechanical, biological or a combination of both.

18F]-sodium fluoride PET-MR imaging reveals bone-cartilage interactions in hip osteoarthritis

18F]-sodium fluoride PET-MR imaging reveals bone-cartilage interactions in hip osteoarthritis

Assessment of clinical significance of ultrasonographic detection ofhyperechogenic deposits in hyaline cartilage in patients with knee osteoarthritis

The aimof the study was to assess the relationship between the detection of hyperechogenic deposits (HD) in the hyaline cartilage of the knee joints (KJ) at ultrasonography in patients with osteoarthritis (OA), clinical manifestations and structural changes according to KJ ultrasonography and radiography.Material and methods.A prospective analysis of clinical, radiological and ultrasonographic data of 114 patients with knee OA was conducted. The patients were divided into two groups: 32 patients with HD detected in at least one of the KJ, and 82 patients without HD; 32 patients of the 1st group and 34 patients of the 2nd group were observed for 2 years. A comparative assessment of initial clinical manifestations (WOMAC index), x-ray data and ultrasonographic parameters of the subchondral bone, hyaline cartilage and the degree of synovial inflammation in the groups of patients at the beginning of the study and after 2 years was carried out. The exclusion criteria were other joint diseases; paroxysmal course of the inflammatory process in KJ; trauma and history of operations on KJ; ESR &gt;20 mm/h, uric acid level &gt;360 μmol/l and C-reactive protein &gt;5 mg/l.Results and discussion.HD in hyaline cartilage was found in 28.1% of patients with knee OA. After 2 years HD remained in all patients having them at inclusion, and in 5.6% of the patients they were found for the first time. In 13 patients with HD in hyaline cartilage, synovial fluid was studied and in all cases calcium pyrophosphate crystals were identified by phase-contrast microscopy. The presence of HD in the hyaline cartilage of patients with knee OA was accompanied by more pronounced ultrasonographic signs of synovitis and was associated with a higher rate of osteophytes growth in the absence of the changes of the hyaline cartilage thickness according to the ultrasonography and the width of the joint space according to x-ray.Conclusion.The presence of HD in the hyaline cartilage of patients with knee OA according to ultrasound examination may be associated with the deposition of calcium pyrophosphate crystals and is associated with persistent synovitis and accelerated growth of osteophytes.

Physiological exercise loading suppresses post-traumatic osteoarthritis progression via an increase in bone morphogenetic proteins expression in an experimental rat knee model.

To evaluate the dose-response relationship of exercise loading in the cartilage-subchondral bone (SB) unit in surgically-induced post-traumatic osteoarthritis (PTOA) of the knee. Destabilized medial meniscus (DMM) surgery was performed on the right knee of 12-week-old male Wistar rats, and sham surgery was performed on the contralateral knee. Four weeks after the surgery, the animals were subjected to moderate (12m/min) or intense (21m/min) treadmill exercises for 30min/day, 5days/week for 4 weeks. PTOA development in articular cartilage and SB was examined using histological and immunohistochemical analyses, micro-computed tomography (micro-CT) analysis, and biomechanical testing at 8 weeks after surgery. Gremlin-1 was injected to determine the role of bone morphogenetic protein (BMP) signaling on PTOA development following moderate exercise. Moderate exercise increased BMP-2, BMP-4, BMP-6, BMP receptor 2, pSmad-5, and inhibitor of DNA binding protein-1 expression in the superficial zone chondrocytes and suppressed cartilage degeneration, osteophyte growth, SB damage, and osteoclast-mediated SB resorption. However, intense exercise had little effect on BMP expression and even caused progression of these osteoarthritis (OA) changes. Gremlin-1 injection following moderate exercise caused progression of the PTOA development down to the level of the non-exercise DMM-operated knee. Exercise regulated cartilage-SB PTOA development in DMM-operated knees in a dose-dependent manner. Our findings shed light on the important role of BMP expression in superficial zone chondrocytes in attenuation of PTOA development following physiological exercise loading. Further studies to support a mechanism by which BMPs would be beneficial in preventing PTOA progression are warranted.

A mouse model for chronic pain-induced increase in ethanol consumption.

Chronic pain conditions are often comorbid with alcohol abuse. "Self-medication" with alcohol introduces a host of problems associated with the abuse of alcohol which over time has the potential of exacerbating the painful condition. Despite the prevalence of chronic pain being associated with alcohol abuse, rodent models which mimic the comorbid conditions are lacking. In this study, we model osteoarthritis (OA) in C57BL/6J mice by surgically destabilizing the medial meniscus (DMM). Sham-operated mice served as controls. Thirteen weeks after surgery, DMM but not sham-operated mice exhibited pronounced incapacitance of the surgically manipulated hind limb compared with the nonsurgically manipulated hind limb. At this time, the mice were exposed to the 2-bottle ethanol choice, beginning with 2.5% with a gradual increasing to 20%. Compared with sham controls, DMM mice consumed more EtOH and preferred EtOH over water at the 20% EtOH concentration. Histological analysis verified that the DMM mice exhibited significant damage to the articular cartilage and osteophyte growth compared with sham controls and these measures of the severity of OA correlated with the amount of ethanol intake. Thus, the combination of the DMM model of OA with the enhanced two-bottle ethanol choice is a potential preclinical approach in mice by which the basis of the comorbid association of alcohol abuse and chronic pain conditions can be explored.

Non-operative management of osteoarthritis of the knee joint.

Osteoarthritis is a chronic disorder of synovial joints in which there is progressive softening and disintegration of articular cartilage accompanied by the growth of osteophytes. Treatment designed for osteoarthritis should aim at reducing pain, improve joint mobility, and limit functional impairment. It can be achieved by pharmacological and non-pharmacological means. Non-operative treatment of OA is useful for patients with KL grade 1-3, which are early stages of OA. However, in an advanced stage of OA (KL grade 4), surgical treatment is needed as definitive treatment.

Integrin α1β1 protects against signs of post-traumatic osteoarthritis in the female murine knee partially via regulation of epidermal growth factor receptor signalling

To investigate the role of integrin α1β1 in the progression of post-traumatic osteoarthritis (PTOA), and elucidate the contribution of epidermal growth factor receptor (EGFR) signalling to the mechanism by which integrin α1β1 might control PTOA. We hypothesised that integrin α1β1 plays a protective role in the course of PTOA and that the effect of PTOA (e.g., synovitis, loss of cartilage and growth of osteophytes) would be exacerbated in mice lacking integrin α1β1 at every time point post destabilisation of medial meniscus (DMM). DMM or sham surgery was performed on integrin α1-null and wild type (WT) mice and the progression of PTOA analysed at 2, 4, 8 and 12 weeks post-surgery (PS) using micro-computed tomography (microCT), histology, and immunohistochemistry. In addition, the effects of EGFR blockade were examined by treating the mice with the EGFR inhibitor erlotinib. Integrin α1-null female, but not male, mice showed earlier cartilage degradation post DMM surgery compared to WT controls. Furthermore, erlotinib treatment resulted in significantly less cartilage damage in integrin α1-null but not WT mice. Independent of genotype, erlotinib treatment significantly mitigated the effects of PTOA on many tissues of female mice including meniscal and fabella bone volume, subchondral bone thickness and density and cartilage degradation. In contrast, reduced EGFR signalling had little effect on signs of PTOA in male mice. Integrin α1β1 protects against PTOA-induced cartilage degradation in female mice partially via the reduction of EGFR signalling. Furthermore, reduction of EGFR signalling protects against the development of PTOA in female, but not male mice.

Therapeutic effects of an anti-ADAMTS-5 antibody on joint damage and mechanical allodynia in a murine model of osteoarthritis

The primary goal of this study was to test the disease-modifying effect of blocking a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-5 with a neutralizing monoclonal antibody (mAb) starting 4 weeks after destabilization of the medial meniscus (DMM) in the mouse. We also investigated whether ADAMTS-5 blockade reversed mechanical allodynia and decreased monocyte chemoattractant protein (MCP)-1 production by dorsal root ganglia (DRG) cells. Ten-week old male C57BL/6 mice underwent DMM surgery and were either left untreated or treated with anti-ADAMTS-5 mAb or IgG2c isotype control mAb starting 4 weeks after surgery. Knees were collected for histopathology 4 or 12 weeks later. Mechanical allodynia was monitored biweekly in the ipsilateral hind paw through 16 weeks. DRG were collected and cultured 8 weeks after DMM for analysis of MCP-1 production. By 4 weeks after DMM, mild cartilage degeneration was evident in the medial compartment, small osteophytes were present, and subchondral bone sclerosis was established. By 16 weeks after surgery, significant cartilage deterioration was apparent on the medial tibial plateaux and medial femoral condyles, osteophyte size had increased, and subchondral bone sclerosis was maintained. Treatment with ADAMTS-5 mAb from week 4 to 16 after surgery slowed cartilage degeneration and osteophyte growth but did not affect subchondral bone sclerosis. Moreover, ADAMTS-5 blockade resulted in temporary reversal of mechanical allodynia, which correlated with decreased MCP-1 production by cultured DRG cells. This study suggests therapeutic efficacy of an ADAMTS-5 mAb in the DMM model, when therapy starts early in disease.

Pivotal role of Sirt6 in the crosstalk among ageing, metabolic syndrome and osteoarthritis

Osteoarthritis (OA) is a chronic degenerative joint disorder commonly associated with metabolic syndrome. As ageing and obesity has a great impact on the initiation/severity of OA, herein we sought to investigate the involvement of Sirt6 in the crosstalk between ageing and metabolic syndrome/OA. Sirt6 haploinsufficiency in mice promoted the expression of inflammatory cytokines in the IPFP. Enhanced inflammation of the IPFP in the aged Sirt6 ± HFD group was paralleled with accelerated OA change, including osteophyte growth and chondrocyte hypertrophy. Conversely, mesenchyme-specific Sirt6-deficient mice revealed both attenuated chondrocyte hypertrophy and proteoglycan synthesis, although chondrocyte senescence was enhanced as shown in the aged WT mice. Thus Sirt6 has key roles in the relationship among ageing, metabolic syndrome, and OA.

A MULTICENTER, BLIND, RANDOMIZED, PLACEBO-CONTROLLED STUDY OF THE SYMPTOM- AND STRUCTURE-MODIFYING EFFET OF ALFLUTOP IN PATIENTS WITH KNEE OSTEOARTHRITIS. REPORT 2: THE ASSESSMENT OF THE STRUCTURE-MODIFYING EFFECT OF THE DRUG

Система комплексной поддержки и сопровождения научного журнала Elpub позволяет запустить двуязычный сайт журнала со встроенной системой электронной редакции в соответствии с лучшими издательскими практиками, а так же предусматривает техническую и методическую поддержку со стороны специалистов НЭИКОН.

The sources of pain in osteoarthritis: a pathophysiological review.

The pain of osteoarthritis (OA) has multifaceted etiologies within and outside the joint. It is believed to be driven by both nociceptive and neuropathic mechanisms, as well as abnormal excitability in the pain pathways of the peripheral and central nervous system. Inflammation in the joint triggers a cascade of events that leads to peripheral sensitization, increased sensitivity of nociceptive primary afferent neurons, and hyperexcitability of the nociceptive neurons in the central nervous system. Pain receptors have been found in the synovium, ligaments, capsule, subchondral bone and surrounding tissues, with the exception of articular cartilage. The bone-related causes of pain in OA include subchondral microfractures, bone stretching with elevation of the periosteum due to osteophyte growth, bone remodeling and repair, bone marrow lesions, and bone angina caused by decreased blood flow and increased intra-osseous pressure. Central factors alter pain processing by setting the gain in such a way that, when a peripheral input is present, it is processed against a background of central factors that can enhance or diminish the experience of pain. As a complex phenomenon with a strong subjective component, pain can also be influenced by the nature of the underlying disease, personal predisposition (biological and psychological), and environmental and psychosocial factors. This review examines the current literature regarding the sources and mechanisms of pain in OA.

THU0278 Total Hip Arthroplasty May not be Needed in Rheumatoid Arthritis Patients with Early “Beak Sign” Given Anti-TNF Therapy

BackgroundRecent clinical trials of biologic agents have reported that radiographic evidence of healing was seen in patients with rheumatoid arthritis (RA) who were in clinical remission. However, those results were...

Genes Leading to Intervertebral Disc Degeneration

Lumbar disc degeneration (LDD) is an important cause of low back pain, which is a common and costly problem worldwide. LDD is characterized by several histological changes in and around the disc, including narrowing and dehydration of the disc, osteophyte growth at the adjacent vertebral body and end plate change. LDD has been shown in many studies to have a heritable basis. Several plausible candidate genes have been explored, and some associations have been replicated.1 More recently, genome-wide association (GWA) studies have become available in which an agnostic search of the genome is performed using multiple variant markers.2 This method aims to identify common variants associated with LDD. We have performed the first GWA meta-analysis of LDD and explored the role of epigenetic influence at the most highly associated marker.3 We have developed a continuous trait based on disc space narrowing and osteophytes growth which is measurable on all forms of imaging (plain radiograph, computed tomographic scan and magnetic resonance imaging) and performed a meta-analysis of five cohorts of Northern European extraction each having GWA data imputed to HapMap vs2. This study of 4,600 individuals identified 4 single nucleotide polymorphisms with p &lt; 5 × 10-8, the threshold set for genome-wide significance. We identified a variant in the PARK2 gene ( p = 2.8 × 10-8) associated with LDD. Examination of methylation using the Illumina 450k chip showed differential methylation at one CpG island of the PARK2 promoter in a subset of subjects from TwinsUK (β = 8.74 × 10-4, p = 0.006). This work provides evidence of association of the PARK2 gene and suggests that methylation of the PARK2 promoter may influence degeneration of the intervertebral disc. This gene has not previously been considered a candidate in LDD but has been reported in juvenile Parkinson disease as well as tumor development. The gene encodes a protein called parkin, is a component of the ubiquitin ligase complex, targeting effete proteins for removal. This study highlights how GWAS is useful at identifying new pathways of pathology—much needed in this difficult to study tissue. In addition, the limitations of the candidate gene approach are increasingly recognized.4 This work required further independent replication, and epigenetic factors are also to be explored further, given that so little of the estimated heritability is accounted for by the genetic variants identified thus far. Finally, ongoing work refining phenotypes will allow large consortia to amass the sample sizes required for robust findings. Disclosure of Interest None declared References Eskola PJ, Lemmelä S, Kjaer P, et al. Genetic association studies in lumbar disc degeneration: a systematic review. PLoS ONE 2012;7(11):e49995 Visscher PM, Brown MA, McCarthy MI, Yang J. Five years of GWAS discovery. Am J Hum Genet 2012;90(1):7–24 Williams FM, Bansal AT, van Meurs JB, et al. Novel genetic variants associated with lumbar disc degeneration in northern Europeans: a meta-analysis of 4600 subjects. Ann Rheum Dis 2013;72(7):1141–1148 Richards JB, Kavvoura FK, Rivadeneira F, et al; Genetic Factors for Osteoporosis Consortium. Collaborative meta-analysis: associations of 150 candidate genes with osteoporosis and osteoporotic fracture. Ann Intern Med 2009;151(8):528–537

Fast-throughput assessment of osteophyte growth in murine osteoarthritis for cross-sectional or longitudinal microct studies

Fast-throughput assessment of osteophyte growth in murine osteoarthritis for cross-sectional or longitudinal microct studies

FK506 protects against articular cartilage collagenous extra-cellular matrix degradation

Osteoarthritis (OA) is a non-rheumatologic joint disease characterized by progressive degeneration of the cartilage extra-cellular matrix (ECM), enhanced subchondral bone remodeling, activation of synovial macrophages and osteophyte growth. Inhibition of calcineurin (Cn) activity through tacrolimus (FK506) in invitro monolayer chondrocytes exerts positive effects on ECM marker expression. This study therefore investigated the effects of FK506 on anabolic and catabolic markers of osteoarthritic chondrocytes in 2D and 3D invitro cultures, and its therapeutic effects in an invivo rat model of OA. Effects of high and low doses of FK506 on anabolic (QPCR/histochemistry) and catabolic (QPCR) markers were evaluated invitro on isolated (2D) and ECM-embedded chondrocytes (explants, 3D pellets). Severe cartilage damage was induced unilaterally in rat knees using papain injections in combination with a moderate running protocol. Twenty rats were treated with FK506 orally and compared to twenty untreated controls. Subchondral cortical and trabecular bone changes (longitudinal microCT) and macrophage activation (SPECT/CT) were measured. Articular cartilage was analyzed exvivo using contrast enhanced microCT and histology. FK506 treatment of osteoarthritic chondrocytes invitro induced anabolic (mainly collagens) and reduced catabolic ECM marker expression. In line with this, FK506 treatment clearly protected ECM integrity invivo by markedly decreasing subchondral sclerosis, less development of subchondral pores, depletion of synovial macrophage activation and lower osteophyte growth. FK506 protected cartilage matrix integrity invitro and invivo. Additionally, FK506 treatment invivo reduced OA-like responses in different articular joint tissues and thereby makes Cn an interesting target for therapeutic intervention of OA.