Osteophytes In Osteoarthritis Research Articles

IL-6 Reduces Spheroid Sizes of Osteophytic Cells Derived from Osteoarthritis Knee Joint via Induction of Apoptosis

Osteophytes in osteoarthritis (OA) joints contribute to restriction of joint movement, joint pain, and OA progression, but little is known about osteophyte regulators. Examination of gene expression related to cartilage extracellular matrix, endochondral ossification, and growth factor signaling in articular cartilage and osteophytes obtained from OA knee joints showed that several genes such as COL1A1, VCAN, BGLAP, BMP8B, RUNX2, and SOST were overexpressed in osteophytes compared with articular cartilage. Ratios of mesenchymal stem/progenitor cells, which were characterized by co-expression of CD105 and CD166, were significantly higher in osteophytic cells than articular cells. A three-dimensional culture method for cartilage and osteophyte cells was developed by modification of cultures of self-assembled spheroid cell organoids (spheroids). These spheroids cultured in the media for mesenchymal stem cells containing transforming growth factor-β3 showed characteristic morphologies and gene expression profiles of articular cartilage and osteophytes, respectively. The effects of IL-1β, tumor necrosis factor-α, and IL-6 on the spheroids of articular and osteophytic cells were studied. To the best of our knowledge, they provide the first evidence that IL-6 suppresses the spheroid size of osteophytic cells by inducing apoptosis and reducing extracellular matrix molecules. These data show that IL-6 is the suppressor of osteophyte growth and suggest that IL-6 expression and/or activity are implicated in the regulation of osteophyte formation in pathologic joints.

Morphometric Analysis of Variations in Pattern of Talar Articular Facets on Calcaneum in North-West India

Calcaneum, the largest tarsal bone forms joint with Talus (Talocalcaneal joint). The superior surface of calcaneum shows three facets for talus. Patterns of facets are variable in different populations. Knowledge of the facets is important for orthopaedic surgeons in correction of foot deformities, as facet number is an important factor in subtalar joint stability and formation of osteophytes in osteoarthritis. The objective of the present study was to identify the patterns of talar facets on calcaneum in North-West India population and their comparison with other population of the world. For the present study; 100 calcanei of unknown age and sex were used. The calcanei were retrieved from the department of Anatomy, at a tertiary care hospital and medical college, in Haryana. The current study will focus on talar articular facets on calcanei. Patterns of talar articular facets on calcanei were observed as described by Bunning and Barnett et al. Present study revealed that pattern I and II were commonly present in the North West population, and accounted for 83% and 16% respectively. The North West population presented Pattern I as the most common pattern as compared to the European population where pattern II was reported as the most common pattern, so variation in the facet pattern between races demand a modification of surgical technique of calcaneal osteotomy to meet the needs of a particular population.

Identification of the skeletal progenitor cells forming osteophytes in osteoarthritis

ObjectivesOsteophytes are highly prevalent in osteoarthritis (OA) and are associated with pain and functional disability. These pathological outgrowths of cartilage and bone typically form at the junction of articular cartilage,...

Multiscale bone quality analysis in osteoarthritic knee joints reveal a role of the mechanosensory osteocyte network in osteophytes

Osteophytes - bony outgrowths on joint structures - are found in healthy individuals but are specifically present in late osteoarthritis (OA). Osteophyte development and function is not well understood, yet biomechanical stimuli are thought to be critical. Bone adapts to mechanical forces via the cellular network of osteocytes. The involvement of osteocytes in osteophyte formation and maturation has not been unravelled. Forty-three osteophytes from tibias of 23 OA patients (65 ± 9 years) were analysed. The trabecular bone structure of osteophytes presented with fewer trabeculae of lower bone mineral density compared to subchondral bone. We identified 40% early stage and 60% late stage osteophytes that significantly differed in their trabecular bone characteristics. Osteophyte bone revealed a higher number of osteocytes and a lower number of empty osteocyte lacunae per bone area than the subchondral bone. We found that OA osteophytes consist of younger bone material comprised of woven and lamellar bone with the capacity to develop into a late stage osteophyte potentially via the involvement of the osteocyte network. Our analysis of OA osteophytes implies a transition from woven to lamellar bone as in physiological bone growth within a pathological joint. Therefore, osteophyte development and growth present a valuable research subject when aiming to investigate the osteogenic signalling cascade.

Advances in the development and influence factors of osteophytes in osteoarthritis

Osteoarthritis (OA) is a common chronic arthritis, mainly suffering the middle and elderly patients, and it is the main cause of arthralgia and articular functional disturbance. Studies have suggested that osteophyte formation was closely connected with the development of OA due to the stabilization of suffered joints and arthralgia induced by osteophytes. In tissue constitution and pathology, osteophyte is made up of bone, cartilage and connective tissue, stemming from MSCs. With the development of osteophytes, the proportion of bone increases while the proportion of cartilage and connective tissue decreases. What's more, in promotion factors of osteophytes, osteophyte formation was induced by the biomechanical and biochemical factors and their both effect. The biomechanical factors result from imbalance of articular biomechanics induced by cartilaginous degeneration and ligament trauma. And the biochemical factors result from alteration of articular microenvironment induced by metabolic disorder of chondrocytes and synovitis. Furthermore, the both effects that the biomechanical factors induces biochemical alterations also co-promote osteophyte formation. And studies on the mechanism indicated that osteophyte formation was regulated by several signaling pathways and cytokines. TGF-β superfamily and Hedgehog signaling pathway were involved in modulating osteophyte formation. TGF-β and BMPs modulated the initiation and late stage of osteophyte formation respectively. And Hedgehog signaling pathway regulated the osteophyte formation with modulating the hypertrophy of chondral osteophytes. This paper emphatically reviews the development and mechanism of osteophytes in OA for deeply understanding the OA and bringing new ideas and methods for the precaution and treatment of OA.

Expression of adipokines in osteoarthritis osteophytes and their effect on osteoblasts

ObjectiveOsteophyte formation in osteoarthritis (OA) is mediated by increased osteoblast activity, which is -in turn- regulated by the Wnt signaling pathway. Obesity is regarded a risk factor in OA, yet little is known about the interaction between adipose tissue-derived factors, the adipokines, and bone formation, although adipokines are associated with the pathogenesis of OA. Therefore, the effect of adipokines on bone and cartilage forming cells and osteophyte development was analyzed. MethodsHuman OA osteophytes were histologically characterized and adipokine expression was evaluated by immunohistochemistry. Osteoblasts and chondrocytes were isolated from OA tissue and stimulated with adiponectin, resistin, or visfatin. Cytokine and osteoblast/chondrocyte markers were quantified and activation of Wnt and p38 MAPK signaling was analyzed. ResultsAdiponectin, resistin, and visfatin were expressed in OA osteophytes by various articular cell types. Stimulation of OA osteoblasts with adiponectin and of OA chondrocytes with visfatin led to an increased release of proinflammatory mediators but not to osteoblast differentiation or activation. Additionally, visfatin increased matrix degrading factors in chondrocytes. Wnt signaling was not altered by adipokines, but adiponectin induced p38 MAPK signaling in osteoblasts. ConclusionAdipokines are present in OA osteophytes, and adiponectin and visfatin increase the release of proinflammatory mediators by osteoblasts and chondrocytes. The effects of adiponectin were mediated by p38 MAPK but not Wnt signaling in osteoblasts. Therefore, the results support the idea that adipokines do not directly influence osteophyte development but the proinflammatory conditions in OA.

Differentiation of osteophyte types in osteoarthritis – proposal of a histological classification

ObjectiveOsteoarthritis is not only characterized by cartilage degradation but also involves subchondral bone remodeling and osteophyte formation. Osteophytes are fibrocartilage-capped bony outgrowths originating from the periosteum. The pathophysiology of osteophyte formation is not completely understood. Yet, different research approaches are under way. Therefore, a histological osteophyte classification to achieve comparable results in osteophyte research was established for application to basic science research questions. MethodsThe osteophytes were collected from knee joints of osteoarthritis patients (n=10, 94 osteophytes in total) after joint replacement surgery. Their size and origin in the respective joint were photo-documented. To develop an osteophyte classification, serial tissue sections were evaluated using histological (hematoxylin and eosin, Masson's trichrome, toluidine blue) and immunohistochemical staining (collagen type II). ResultsBased on the histological and immunohistochemical evaluation, osteophytes were categorized into four different types depending on the degree of ossification and the percentage of mesenchymal connective tissue. Size and localization of osteophytes were independent from the histological stages. ConclusionThis histological classification system of osteoarthritis osteophytes provides a helpful tool for analyzing and monitoring osteophyte development and for characterizing osteophyte types within a single human joint and may therefore contribute to achieve comparable results when analyzing histological findings in osteophytes.

Alpha C-telopeptide of type I collagen is associated with subchondral bone turnover and predicts progression of joint space narrowing and osteophytes in osteoarthritis.

To evaluate joint tissue remodeling using the urinary collagen biomarkers urinary α-C-telopeptide of type I collagen (α-CTX) and urinary C-telopeptide of type II collagen (CTX-II) and to determine the association of these biomarkers with osteoarthritis (OA) severity, progression, and localized knee bone turnover. Participants (n = 149) with symptomatic and radiographic knee OA underwent fixed-flexion knee radiography at baseline and 3 years, and late-phase bone scintigraphy of both knees at baseline, which were scored semiquantitatively for osteophyte and joint space narrowing (JSN) severity and uptake intensity, with scores summed across knees. Urinary concentrations of α-CTX and CTX-II were determined by enzyme-linked immunosorbent assay. Immunohistochemical analysis of human OA knees was performed to localize the joint tissue origin of the biomarker epitopes. Urinary α-CTX concentrations correlated strongly with the intensity of bone scintigraphic uptake and with JSN progression (risk ratio 13.2) and osteophyte progression (risk ratio 3). Urinary CTX-II concentrations were strongly associated with intensity of bone scintigraphic uptake, with JSN and osteophyte severity, and with OA progression based on osteophyte score. Urinary α-CTX localized primarily to high bone turnover areas in subchondral bone. CTX-II localized to the bone-cartilage interface, the tidemark, and damaged articular cartilage. Baseline urinary α-CTX, which was localized to high turnover areas of subchondral bone, was associated with dynamic bone turnover of knees, as signified by scintigraphy, and progression of both osteophytes and JSN. Urinary CTX-II correlated with JSN and osteophyte severity and progression of osteophytes. To our knowledge, this represents the first report of serologic markers reflecting subchondral bone turnover. These collagen markers may be useful for noninvasive detection and quantification of active subchondral bone turnover and joint remodeling in knee OA.

A remarkable case of hypertrophic pseudoarthrosis of the pars interarticularis in a young American football professional player.

Lumbar spondylolysis is a defect of the pars interarticularis regarded as a stress fracture. The bone stump around the pars defect usually appears atrophic and is fibrously united or filled with fibro cartilaginous mass, similar to long bone pseudoarthrosis. Lumbar spondylolysis sometimes causes bone growth resembling that of an osteophyte in osteoarthritis, and in elderly patients, the ragged edges result in radiculopathy around the defect. However, lumbar spondylolysis is rarely reported to cause hypertrophic changes resulting in spinal canal stenosis in young patients. In this report, we present an unprecedented radiological finding of distinctive hypertrophic change around the pars defect, which occurred in a young professional football player.

Asporin and transforming growth factor-β gene expression in osteoblasts from subchondral bone and osteophytes in osteoarthritis

BackgroundTo clarify the significance of subchondral bone and osteophytes in the pathology of osteoarthritis (OA), we investigated the expression of asporin (ASPN), transforming growth factor-β1 (TGF-β1), TGF-β2, TGF-β3, and runt-related transcription factor-2 (Runx2) genes involved in bone metabolism. MethodsOsteoblasts were isolated from 19 patients diagnosed with knee OA and from 4 patients diagnosed with femoral neck fracture. Osteoblast expression of mRNA encoding ASPN, TGF-βi, TGF-β2, TGF-β3, and Runx2 was analyzed using real-time RT-PCR. ResultsExpression of ASPN, TGF-β1, and TGF-β3 mRNA in the subchondral bone and osteophytes of OA patients increased compared with that of non-OA patients. The ratio of ASPN to TGF-β1 mRNA in patients with severe cartilage damage was higher than that in patients with mild cartilage damage. ConclusionsThe increased ratio of ASPN mRNA to TGF-β1 mRNA in patients with severe relative to mild cartilage damage indicates that increased ASPN mRNA expression was significantly associated with the severity of cartilage degeneration. This finding suggests that ASPN may regulate TGF-β1-mediated factors in the development of OA, which may provide clues as to the underlying pathology of OA.

Resemblance of osteophytes in experimental osteoarthritis to transforming growth factor β–induced osteophytes: Limited role of bone morphogenetic protein in early osteoarthritic osteophyte formation

Osteoarthritis (OA) is characterized by cartilage damage, synovial fibrosis, and osteophyte formation. Both transforming growth factor beta (TGFbeta) and bone morphogenetic protein 2 (BMP-2) can induce the formation of osteophytes during OA, but their specific role in this process is unclear. The purpose of this study was to investigate the respective contributions of TGFbeta and BMP-2 to OA. Mouse knee joints injected with adenovirus (Ad-TGFbeta or Ad-BMP-2) were compared histologically with knee joints from murine models of OA (joints injected with collagenase and joints from STR/Ort mice with spontaneous OA). To further investigate the role of BMP during osteophyte formation, adenovirus Ad-Gremlin was injected into knee joints that had previously been injected with Ad-TGFbeta or collagenase. BMP-2 induced early osteophytes, which bulged from the growth plates on the femur and grew on top of the patella, whereas TGFbeta induced early osteophyte formation on the bone shaft beneath the collateral ligament on the femur as well as on top of the patella. The pattern of osteophyte formation during experimental OA closely resembled that of TGFbeta-induced osteophyte formation, but differed from the pattern induced by BMP-2. Ad-Gremlin proved to be able to totally block BMP-2-induced osteophyte formation. However, blocking BMP activity inhibited neither TGFbeta-induced nor experimental OA-associated osteophyte formation. Our findings demonstrate that the role of BMP during the onset of TGFbeta-induced and experimental OA-induced osteophyte formation is limited. The latter finding does not rule out a role of BMP during osteophyte maturation.

Neurovascular invasion at the osteochondral junction and in osteophytes in osteoarthritis

Background:Normal adult articular cartilage is thought to be avascular and aneural.Objective:To describe neurovascular structures at the osteochondral junction and in osteophytes in tibiofemoral osteoarthritis (OA) displaying a range of severity...

A comparison of the semiflexed (MTP) view with the standing extended view (SEV) in the radiographic assessment of knee osteoarthritis in a busy routine X-ray department

To compare the reproducibility of the standing extended view (SEV) (also known as the standing anteroposterior view) with the semiflexed, postero-anterior view [the 'metatarsophalangeal' (MTP)] view for assessing joint space width (JSW) and osteophytes in osteoarthritis of the knee when used in a busy routine X-ray department. Forty-seven patients (24 men) had both SEV and MTP views taken on the same day in a busy National Health Service radiography department. Repeat views were taken as entirely separate procedures some time over the following 2 weeks, in the same department and with no special arrangements for the selection of radiographers, time of day, or X-ray machine. The first 24 patients had second views in the SEV position whilst the remaining 23 had second MTP views. Radiographs were read independently by two experienced observers who measured JSW with a transparent ruler to the nearest 0.5 mm at the narrowest point in both medial and lateral compartments of the tibiofemoral joint in both knees. Osteophytes were graded 0-2 according to a standard atlas. Ten SEV and 10 MTP radiographs selected randomly were re-read by one observer. Mean (95% confidence interval) JSW in the medial compartment measured on SEV radiographs was 3.54 mm (3.08, 3.99) and on MTP radiographs it was 2.80 mm (2.37, 3.23); in the lateral compartment it was 6.04 mm (5.71, 6.37) when measured on SEV radiographs and 5.47 mm (5.09, 5.85) on MTP radiographs. The estimated variances for the medial compartment were 2.0 mm2 for SEV and 0.2 mm2 for MTP (P < 0.001) and for the lateral compartment 1.4 mm2 for SEV and 0.5 mm2 for MTP (P < 0.001). The proportion of radiographs for which there was disagreement between observers regarding osteophyte grade was not statistically different between SEV and MTP views (SEV, medial 40%, lateral 44%; MTP, medial 39%, lateral 39%). Even when radiographs are taken in a busy National Health Service radiography department, measurement of JSW from the MTP view is more reproducible than from the SEV view, the MTP view gives a slightly lower measurement of JSW, and there is no advantage in using either view in recording osteophyte grade. We recommend the wider adoption of the MTP method.

Anatomico-radiological study of an ununited intracapsular fracture of the femoral neck dating back 47 years

This is the anatomico-radiological study of a 47-year-old ununited intracapsular fracture of the hip. The femoral head was osteoporotic but its center contained a zone of osteomedullary necrosis in the form of a bone infarct. Its contour was reshaped and remnants of articular cartilage were covered by osteophyte-like bone formations; furthermore, an acetabular osteophyte was observed. Histological signs of Paget's disease of the bone were observed in the medial part of the femoral stump. The findings in this case provide the basis for a discussion of the pathogenesis of osteophytes in osteoarthritis, the pathogenesis of bone infarcts (and the distinction between this condition and another form of aseptic osteonecrosis), and the role of mechanical stresses in the development of Paget's disease of the bone.