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Journal of Orthopaedic Surgery (Hong... Dec 2016An osteophyte is a fibrocartilage-capped bony outgrowth that is one of the features of osteoarthritis. This study reviewed the types, risk factors, pathophysiology,... (Review)
Review
An osteophyte is a fibrocartilage-capped bony outgrowth that is one of the features of osteoarthritis. This study reviewed the types, risk factors, pathophysiology, clinical presentations, and medical and surgical treatment of osteophytes. Extraspinal osteophytes are classified as marginal, central, periosteal, or capsular, whereas vertebral osteophytes are classified as traction or claw. Risk factors for development of osteophytes include age, body mass index, physical activity, and other genetic and environmental factors. Transforming growth factor β plays a role in the pathophysiology of osteophyte formation. Osteophytes can cause pain, limit range of motion, affect quality of life, and cause multiple symptoms at the spine. Medical treatment involves the use of bisphosphonates and other non-steroidal anti-inflammatory agents. Surgical treatment in the form of cheilectomy for impingement syndromes during joint replacement is recommended.
Topics: Humans; Osteophyte
PubMed: 28031516
DOI: 10.1177/1602400327 -
Aging Dec 2020Osteoarthritis is a chronic degenerative disease that can lead to restricted activity or even disability. Bone marrow mesenchymal stem cells can repair cartilage damage...
Osteoarthritis is a chronic degenerative disease that can lead to restricted activity or even disability. Bone marrow mesenchymal stem cells can repair cartilage damage and treat osteoarthritis via cell therapies or in-tissue engineering. Research has shown that the paracrine mechanism is the main mode of action of mesenchymal stem cells. Exosomes are the smallest known membrane-bound nanovesicles. Exosomes are also important carriers of paracrine delivery agents and promote communication between cells. We demonstrated that bone marrow mesenchymal stem cell-derived exosomes can delay the progression of osteoarthritis. Exosomes alleviate cartilage damage, reduce osteophyte formation and synovial macrophage infiltration, inhibit M1 macrophage production and promote M2 macrophage generation. In synovial fluid, the expression levels of the proinflammatory cytokines, IL-1β, IL-6, and TNF-α were decreased and the release of the anti-inflammatory cytokine, IL-10 was increased. , macrophages treated with exosomes maintain chondrocytes' chondrogenic characteristics and inhibit hypertrophy. Our results demonstrated that bone marrow mesenchymal stem cell-derived exosomes may relieve osteoarthritis by promoting the phenotypic transformation of synovial macrophages from M1 to M2.
Topics: Animals; Anterior Cruciate Ligament; Cartilage, Articular; Chondrocytes; Disease Models, Animal; Exosomes; Hypertrophy; Injections, Intra-Articular; Interleukin-10; Interleukin-1beta; Interleukin-6; Macrophages; Menisci, Tibial; Mesenchymal Stem Cells; Mice; Osteoarthritis; Osteophyte; Phenotype; RAW 264.7 Cells; Rats; Synovial Fluid; Synovial Membrane; Tumor Necrosis Factor-alpha
PubMed: 33350983
DOI: 10.18632/aging.104110 -
Annals of the Rheumatic Diseases Dec 2020Osteophytes are highly prevalent in osteoarthritis (OA) and are associated with pain and functional disability. These pathological outgrowths of cartilage and bone...
OBJECTIVES
Osteophytes 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, periosteum and synovium. The aim of this study was to identify the cells forming osteophytes in OA.
METHODS
Fluorescent genetic cell-labelling and tracing mouse models were induced with tamoxifen to switch on reporter expression, as appropriate, followed by surgery to induce destabilisation of the medial meniscus. Contributions of fluorescently labelled cells to osteophytes after 2 or 8 weeks, and their molecular identity, were analysed by histology, immunofluorescence staining and RNA in situ hybridisation. mice and mice crossed with multicolour reporter mice were used for identification and clonal tracing of mesenchymal progenitors. Mice carrying , , , , or were crossed with tdTomato reporter mice to lineage-trace chondrocytes and stem/progenitor cell subpopulations.
RESULTS
Articular chondrocytes, or skeletal stem cells identified by , or expression, did not give rise to osteophytes. Instead, osteophytes derived from -expressing stem/progenitor cells in periosteum and synovium that are descendants from the -expressing embryonic joint interzone. Further, we show that -expressing progenitors in periosteum supplied hybrid skeletal cells to the early osteophyte, while -expressing progenitors from synovial lining contributed to cartilage capping the osteophyte, but not to bone.
CONCLUSION
Our findings reveal distinct periosteal and synovial skeletal progenitors that cooperate to form osteophytes in OA. These cell populations could be targeted in disease modification for treatment of OA.
Topics: Animals; Cell Lineage; Mice; Osteoarthritis; Osteophyte; Periosteum; Stem Cells; Synovial Membrane
PubMed: 32963046
DOI: 10.1136/annrheumdis-2020-218350 -
Annals of the Rheumatic Diseases Nov 2023Prior studies noted that chondrocyte SIRT6 activity is repressed in older chondrocytes rendering cells susceptible to catabolic signalling events implicated in...
OBJECTIVES
Prior studies noted that chondrocyte SIRT6 activity is repressed in older chondrocytes rendering cells susceptible to catabolic signalling events implicated in osteoarthritis (OA). This study aimed to define the effect of deficiency on the development of post-traumatic and age-associated OA in mice.
METHODS
Male cartilage-specific -deficient mice and intact controls underwent destabilisation of the medial meniscus (DMM) or sham surgery at 16 weeks of age and OA severity was analysed at 6 and 10 weeks postsurgery. Age-associated OA was assessed in mice aged 12 and 18 months of age. OA severity was analysed by micro-CT, histomorphometry and scoring of articular cartilage structure, toluidine blue staining and osteophyte formation. SIRT6-regulated pathways were analysed in human chondrocytes by RNA-sequencing, qRT-PCR and immunoblotting.
RESULTS
deficient mice displayed enhanced DMM-induced OA severity and accelerated age-associated OA when compared with controls, characterised by increased cartilage damage, osteophyte formation and subchondral bone sclerosis. In chondrocytes, RNA-sequencing revealed that depletion significantly repressed cartilage extracellular matrix (eg, ) and anabolic growth factor (eg, insulin-like growth factor-1 ()) gene expression. Gain-of-function and loss-of-function studies in chondrocytes demonstrated that SIRT6 depletion attenuated, whereas adenoviral overexpression or MDL-800-induced activation promoted IGF-1 signalling by increasing Akt phosphorylation.
CONCLUSIONS
SIRT6 deficiency increases post-traumatic and age-associated OA severity in vivo. SIRT6 profoundly regulated the pro-anabolic and pro-survival IGF-1/Akt signalling pathway and suggests that preserving the SIRT6/IGF-1/Akt axis may be necessary to protect cartilage from injury-associated or age-associated OA. Targeted therapies aimed at increasing SIRT6 function could represent a novel strategy to slow or stop OA.
Topics: Male; Animals; Mice; Humans; Aged; Insulin-Like Growth Factor I; Osteophyte; Proto-Oncogene Proteins c-akt; Osteoarthritis; Chondrocytes; Cartilage, Articular; RNA; Sirtuins; Disease Models, Animal
PubMed: 37550003
DOI: 10.1136/ard-2023-224385 -
Osteoarthritis and Cartilage Jul 2020To evaluate progression of individual radiographic features 5 years following exercise therapy or arthroscopic partial meniscectomy as treatment for degenerative... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To evaluate progression of individual radiographic features 5 years following exercise therapy or arthroscopic partial meniscectomy as treatment for degenerative meniscal tear.
DESIGN
Randomized controlled trial including 140 adults, aged 35-60 years, with a magnetic resonance image verified degenerative meniscal tear, and 96% without definite radiographic knee osteoarthritis. Participants were randomized to either 12-weeks of supervised exercise therapy or arthroscopic partial meniscectomy. The primary outcome was between-group difference in progression of tibiofemoral joint space narrowing and marginal osteophytes at 5 years, assessed semi-quantitatively by the OARSI atlas. Secondary outcomes included incidence of radiographic knee osteoarthritis and symptomatic knee osteoarthritis, medial tibiofemoral fixed joint space width (quantitatively assessed), and patient-reported outcome measures. Statistical analyses were performed using a full analysis set. Per protocol and as treated analysis were also performed.
RESULTS
The risk ratios (95% CI) for progression of semi-quantitatively assessed joint space narrowing and medial and lateral osteophytes for the surgery group were 0.89 (0.55-1.44), 1.15 (0.79-1.68) and 0.77 (0.42-1.42), respectively, compared to the exercise therapy group. In secondary outcomes (full-set analysis) no statistically significant between-group differences were found.
CONCLUSION
The study was inconclusive with respect to potential differences in progression of individual radiographic features after surgical and non-surgical treatment for degenerative meniscal tear. Further, we found no strong evidence in support of differences in development of incident radiographic knee osteoarthritis or patient-reported outcomes between exercise therapy and arthroscopic partial meniscectomy.
TRIAL REGISTRATION
www.clinicaltrials.gov (NCT01002794).
Topics: Adult; Disease Progression; Exercise Therapy; Female; Follow-Up Studies; Humans; Magnetic Resonance Imaging; Male; Meniscectomy; Middle Aged; Osteoarthritis, Knee; Osteophyte; Patient Reported Outcome Measures; Physical Therapy Modalities; Tibial Meniscus Injuries
PubMed: 32184135
DOI: 10.1016/j.joca.2020.01.020 -
Lancet (London, England) Jan 2018Arthroscopic sub-acromial decompression (decompressing the sub-acromial space by removing bone spurs and soft tissue arthroscopically) is a common surgery for... (Randomized Controlled Trial)
Randomized Controlled Trial
Arthroscopic subacromial decompression for subacromial shoulder pain (CSAW): a multicentre, pragmatic, parallel group, placebo-controlled, three-group, randomised surgical trial.
BACKGROUND
Arthroscopic sub-acromial decompression (decompressing the sub-acromial space by removing bone spurs and soft tissue arthroscopically) is a common surgery for subacromial shoulder pain, but its effectiveness is uncertain. We did a study to assess its effectiveness and to investigate the mechanism for surgical decompression.
METHODS
We did a multicentre, randomised, pragmatic, parallel group, placebo-controlled, three-group trial at 32 hospitals in the UK with 51 surgeons. Participants were patients who had subacromial pain for at least 3 months with intact rotator cuff tendons, were eligible for arthroscopic surgery, and had previously completed a non-operative management programme that included exercise therapy and at least one steroid injection. Exclusion criteria included a full-thickness torn rotator cuff. We randomly assigned participants (1:1:1) to arthroscopic subacromial decompression, investigational arthroscopy only, or no treatment (attendance of one reassessment appointment with a specialist shoulder clinician 3 months after study entry, but no intervention). Arthroscopy only was a placebo as the essential surgical element (bone and soft tissue removal) was omitted. We did the randomisation with a computer-generated minimisation system. In the surgical intervention groups, patients were not told which type of surgery they were receiving (to ensure masking). Patients were followed up at 6 months and 1 year after randomisation; surgeons coordinated their waiting lists to schedule surgeries as close as possible to randomisation. The primary outcome was the Oxford Shoulder Score (0 [worst] to 48 [best]) at 6 months, analysed by intention to treat. The sample size calculation was based upon a target difference of 4·5 points (SD 9·0). This trial has been registered at ClinicalTrials.gov, number NCT01623011.
FINDINGS
Between Sept 14, 2012, and June 16, 2015, we randomly assigned 313 patients to treatment groups (106 to decompression surgery, 103 to arthroscopy only, and 104 to no treatment). 24 [23%], 43 [42%], and 12 [12%] of the decompression, arthroscopy only, and no treatment groups, respectively, did not receive their assigned treatment by 6 months. At 6 months, data for the Oxford Shoulder Score were available for 90 patients assigned to decompression, 94 to arthroscopy, and 90 to no treatment. Mean Oxford Shoulder Score did not differ between the two surgical groups at 6 months (decompression mean 32·7 points [SD 11·6] vs arthroscopy mean 34·2 points [9·2]; mean difference -1·3 points (95% CI -3·9 to 1·3, p=0·3141). Both surgical groups showed a small benefit over no treatment (mean 29·4 points [SD 11·9], mean difference vs decompression 2·8 points [95% CI 0·5-5·2], p=0·0186; mean difference vs arthroscopy 4·2 [1·8-6·6], p=0·0014) but these differences were not clinically important. There were six study-related complications that were all frozen shoulders (in two patients in each group).
INTERPRETATION
Surgical groups had better outcomes for shoulder pain and function compared with no treatment but this difference was not clinically important. Additionally, surgical decompression appeared to offer no extra benefit over arthroscopy only. The difference between the surgical groups and no treatment might be the result of, for instance, a placebo effect or postoperative physiotherapy. The findings question the value of this operation for these indications, and this should be communicated to patients during the shared treatment decision-making process.
FUNDING
Arthritis Research UK, the National Institute for Health Research Biomedical Research Centre, and the Royal College of Surgeons (England).
Topics: Acromion; Adult; Arthroscopy; Decompression, Surgical; England; Exercise Therapy; Female; Humans; Male; Middle Aged; Osteophyte; Shoulder Pain; Treatment Outcome
PubMed: 29169668
DOI: 10.1016/S0140-6736(17)32457-1 -
Current Opinion in Pharmacology Jun 2016Osteoarthritis (OA) is a degenerative joint disease and the most common form of arthritis. Characterised by articular cartilage loss, subchondral bone thickening and... (Review)
Review
Osteoarthritis (OA) is a degenerative joint disease and the most common form of arthritis. Characterised by articular cartilage loss, subchondral bone thickening and osteophyte formation, the OA joint afflicts much pain and disability. Whilst OA has been associated with many contributing factors, its underpinning molecular mechanisms are, nevertheless, not fully understood. Clinical management of OA is largely palliative and there is an ever growing need for an effective disease modifying treatment. This review discusses some of the recent progress in OA therapies in the different joint tissues affected by OA pathology.
Topics: Animals; Antirheumatic Agents; Cartilage, Articular; Drug Design; Humans; Osteoarthritis; Osteophyte; Pain
PubMed: 26921602
DOI: 10.1016/j.coph.2016.02.009 -
International Journal of Clinical and... 2022In this study, we used a canine high-energy fracture model to examine the relationship between the early inflammatory reaction in adjacent tissues and the ability for...
OBJECTIVES
In this study, we used a canine high-energy fracture model to examine the relationship between the early inflammatory reaction in adjacent tissues and the ability for osteophyte growth, aiming to identify causes that lead to atrophic nonunion inflammatory disease and to provide new strategies for prevention and treatment.
MATERIALS AND METHODS
Forty-eight models of canine femoral high energy fractures were prepared and randomly divided into groups A and B (n=24 in each group). Dogs in both groups underwent open reduction and 6-hole plate internal fixation. Group A models were re-opened, and muscle near the bone was scraped at 14 d after the operation. On days 3, 17, 28, and 42 after fracture, 6 experimental dogs were euthanized per group, and the fracture specimens were used to examine pathologic changes and the growth of callus in the fractured end and its adjacent tissues.
RESULTS
At day 14, neutrophil infiltration, with no macrophage recruitment, no mesenchymal cell proliferation, and no fracture healing cascade were observed in the adjacent tissues of both groups. Immediately after the second injury was performed in group A, many macrophages were seen, and mesenchymal cells proliferated, which initiated vigorous osteophyte growth and led to osteophyte healing. Atrophic nonunion was observed in group B without secondary injury.
CONCLUSION
Macrophage recruitment deficiency in adjacent soft tissue in early surgery for high-energy fractures may be an important cause of atrophic nonunion. Secondary injury inflammation can effectively recruit mononuclear macrophages, generate osteoclasts, re-initiate the growth of osteophytes, and promote fracture healing.
PubMed: 35414845
DOI: No ID Found -
Osteoarthritis and Cartilage Mar 2022Osteoarthritis (OA) pathogenesis involves the interaction of articular cartilage with surrounding tissues, which are innervated by tyrosine hydroxylase-positive (TH+)...
OBJECTIVE
Osteoarthritis (OA) pathogenesis involves the interaction of articular cartilage with surrounding tissues, which are innervated by tyrosine hydroxylase-positive (TH+) sympathetic nerve fibers suggesting a role of the sympathetic nervous system (SNS) during OA progression. We analyzed the effects of sympathectomy (Syx) in a murine OA model.
METHODS
Peripheral Syx was generated by 6-hydroxydopamine (6-OHDA) injections in male C57BL/6 mice. OA was induced in wild-type (WT) and Syx mice by destabilization of the medial meniscus (DMM). TH+ fibers and splenic NE were analyzed to evaluate Syx efficiency. OA progression was examined by OARSI and synovitis scores and micro-CT. Expression of TH, α2A- and β2-adrenergic receptors (AR), and activity of osteoblasts (ALP) and osteoclasts (TRAP) was investigated by stainings.
RESULTS
Syx resulted in synovial TH+ fiber elimination and splenic NE decrease. Cartilage degradation and synovitis after DMM were comparably progressive in both WT and Syx mice. Calcified cartilage (CC) and subchondral bone plate (SCBP) thickness and bone volume fraction (BV/TV) increased in Syx mice due to increased ALP and decreased TRAP activities compared to WT 8 weeks after DMMWT and Syx mice developed osteophytes and meniscal ossicles without any differences between the groups. AR numbers decreased in cartilage but increased in synovium and osteophyte regions after DMM in both WT and Syx mice.
CONCLUSION
Peripheral dampening of SNS activity aggravated OA-specific cartilage calcification and subchondral bone thickening but did not influence cartilage degradation and synovitis. Therefore, SNS might be an attractive target for the development of novel therapeutic strategies for pathologies of the subchondral bone.
Topics: Animals; Cartilage Diseases; Disease Models, Animal; Inflammation; Male; Mice; Mice, Inbred C57BL; Osteoarthritis, Knee; Sympathectomy; Synovial Membrane; Tibial Meniscus Injuries
PubMed: 34864169
DOI: 10.1016/j.joca.2021.11.016