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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 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 -
Radiologic Clinics of North America Jul 2022Hip osteoarthritis (OA) is a disease process that impacts the aging population. OA of the hip is the result of degeneration of the articular cartilage, underlying bone... (Review)
Review
Hip osteoarthritis (OA) is a disease process that impacts the aging population. OA of the hip is the result of degeneration of the articular cartilage, underlying bone and soft tissue structures. Radiography is the first-line modality for imaging OA. Radiographic assessment includes imaging features of joint space narrowing, sclerosis, osteophytes, and bony deformities. CT can provide detailed evaluation of the hip with multiplanar reformats. MRI can assess bone marrow signal, articular cartilage damage, and labral abnormalities. Other disease process may appear similar or present concurrently with OA, such as osteonecrosis, rapidly progressive arthritis, and inflammatory and infectious arthropathies.
Topics: Aged; Cartilage, Articular; Humans; Magnetic Resonance Imaging; Osteoarthritis, Hip; Osteophyte; Radiography
PubMed: 35672094
DOI: 10.1016/j.rcl.2022.03.005 -
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 -
World Neurosurgery Apr 2021Bow hunter's syndrome is due to vertebrobasilar insufficiency caused by rotational compression of the vertebral artery. We report a case in which an osteophyte...
Bow hunter's syndrome is due to vertebrobasilar insufficiency caused by rotational compression of the vertebral artery. We report a case in which an osteophyte compressed the left vertebral artery causing cerebellar stroke. The patient underwent successful resection of the osteophyte via anterior surgical approach, and his symptoms of headache and dizziness dissipated postoperatively. This unique syndrome has been treated with multiple modalities and must remain in the clinician's differential as a treatable cause of stroke.
Topics: Cerebellar Diseases; Decompression, Surgical; Diffusion Magnetic Resonance Imaging; Dizziness; Headache; Humans; Male; Middle Aged; Osteophyte; Stroke; Syndrome; Treatment Outcome; Vertebrobasilar Insufficiency
PubMed: 33476780
DOI: 10.1016/j.wneu.2021.01.030 -
Arthritis Research & Therapy Dec 2023While joint immobilization is a useful repair method for intra-articular ligament injury and periarticular fracture, prolonged joint immobilization can cause multiple...
OBJECTIVE
While joint immobilization is a useful repair method for intra-articular ligament injury and periarticular fracture, prolonged joint immobilization can cause multiple complications. A better understanding how joint immobilization and remobilization impact joint function and homeostasis will help clinicians develop novel strategies to reduce complications.
DESIGN
We first determined the effects of long-term immobilization on joint pain and osteophyte formation in patients after an extraarticular fracture or ligament injury. We then developed a mouse model of joint immobilization and harvested the knee joint samples at 2, 4, and 8 weeks. We further determined the effects of remobilization on recovery of the osteoarthritis (OA) lesions induced by immobilization in mice.
RESULTS
We found that the long-term (6 weeks) joint immobilization caused significant joint pain and osteophytes in patients. In mice, 2-week immobilization already induced moderate sensory innervation and increased pain sensitivity and infiltration in synovium without inducing marked osteophyte formation and cartilage loss. Long-term immobilization (4 and 8 weeks) induced more severe sensory innervation and inflammatory infiltration in synovium, massive osteophyte formation on both sides of the femoral condyle, and the edge of the tibial plateau and significant loss of the articular cartilage in mice. Remobilization, which ameliorates normal joint load and activity, restored to certain extent some of the OA lesions and joint function in mice.
CONCLUSIONS
Joint immobilization caused multiple OA-like lesions in both mice and humans. Joint immobilization induced progressive sensory innervation, synovitis, osteophyte formation, and cartilage loss in mice, which can be partially ameliorated by remobilization.
Topics: Humans; Mice; Animals; Osteophyte; Knee Joint; Osteoarthritis; Disease Models, Animal; Cartilage, Articular; Arthralgia
PubMed: 38062473
DOI: 10.1186/s13075-023-03223-3 -
Clinics in Podiatric Medicine and... Jul 2023Arthroscopic reduction of tibiotalar osteophytes results in good to excellent results in the vast majority of patients. Pain is primarily due to synovial hypertrophy and... (Review)
Review
Arthroscopic reduction of tibiotalar osteophytes results in good to excellent results in the vast majority of patients. Pain is primarily due to synovial hypertrophy and anterior tibiotalar entrapment associated with the osteophytes. Osteophytes may be due to repetitive trauma such as sports, or associated with subtle or overt ankle instability. A minimally invasive approach results in rapid recovery and less risk than open interventions. In cases where anterior osteophytes have coexisting ankle instability and in many cases ancillary procedures such as ankle stabilization are performed.
Topics: Humans; Ankle; Osteophyte; Ankle Joint; Arthroscopy; Joint Instability
PubMed: 37236678
DOI: 10.1016/j.cpm.2022.12.001 -
International Journal of Rheumatic... Aug 2022This study describes the characteristics of vertebral osteophytes in different inflammatory and non-inflammatory diseases aiming to reflect the aortic-vertebrae...
OBJECTIVES
This study describes the characteristics of vertebral osteophytes in different inflammatory and non-inflammatory diseases aiming to reflect the aortic-vertebrae interaction.
METHODS
We conducted a cross-sectional study including 4 group of patients, ankylosing spondylitis (AS, n = 52), Takayasu's arteritis (TKA, n = 31), diffuse idiopathic skeletal hyperostosis (DISH, n = 30), coronary artery disease (CAD, n = 10), 100 and also age-matched healthy controls (HC, n = 143). All subjects underwent a chest computed tomography scan and images of the upper and lower border of 7 adjacent thoracic vertebrae (T5 to T12) were captured. An "aorta ipsilateral ratio" (AIR) of the osteophyte was calculated as the area across the midline toward the aorta side divided by the total osteophyte area.
RESULTS
The frequency of subjects with osteophytes and osteophyte counts increased with age across the board. Frequencies of osteophytes in AS and TKA were much higher than age-matched HCs. The AIRs were significantly elevated in AS, TKA and CAD compared with DISH or age-matched HCs. In addition, the AIR of patients with higher C-reactive protein levels (>8 mg/L) were greater than those with lower levels, both among AS and CAD patients.
CONCLUSIONS
Our findings indicate that, in an inflammatory niche, regardless of the origin or the grade of the inflammation, ossification will be facilitated and screwed toward the aorta. There is a possible mechanistic connection between large vessel and new bone formation in the context of inflammation.
Topics: Aorta; Cross-Sectional Studies; Humans; Hyperostosis, Diffuse Idiopathic Skeletal; Inflammation; Osteogenesis; Osteophyte; Thoracic Vertebrae
PubMed: 35694775
DOI: 10.1111/1756-185X.14366 -
The American Journal of Sports Medicine Jun 2023Mechanical loading and alendronate (ALN) can be used as noninvasive physical therapy methods for osteoarthritis (OA). However, the timing and efficacy for treatments are...
BACKGROUND
Mechanical loading and alendronate (ALN) can be used as noninvasive physical therapy methods for osteoarthritis (OA). However, the timing and efficacy for treatments are unknown.
PURPOSE
To determine whether the timing of mechanical loading and ALN influences the pathobiological changes of OA.
STUDY DESIGN
Controlled laboratory study.
METHODS
Mice with OA induced by anterior cruciate ligament transection were subjected to early (1-3 weeks) or late (5-7 weeks) axial compressive dynamic load or intraperitoneal injection of ALN. Changes in gait were analyzed using gait analysis system, pathobiological changes in subchondral bone, cartilage, osteophyte, and synovitis were assessed using micro-computed tomography, tartrate-resistant acid phosphatase staining, pathologic section staining, and immunohistochemistry at 1, 2, 4, and 8 weeks.
RESULTS
At 1, 2, and 4 weeks, the OA limb had lower mean footprint pressure intensity, lower bone volume per tissue volume (BV/TV) in the subchondral bone, and more osteoclasts. At 4 weeks, the early loading, ALN, and load + ALN treatments induced less cartilage destruction, with a corresponding reduction in Osteoarthritis Research Society International score and increased hyaline cartilage thickness. The treatments also resulted in fewer osteoclasts and higher BV/TV and bone mineral density of subchondral bone and suppressed inflammation and interleukin 1β- and tumor necrosis factor α-positive cells in synovium. At 8 weeks, early loading or load + ALN improved the mean footprint pressure intensity and knee flexion. At 8 weeks, early load + ALN had a synergistic effect on protecting hyaline cartilage and proteoglycans. Footprint pressure intensity and cartilage destruction were worse in late loading limbs, and no differences in BV/TV, bone mineral density, osteophyte formation, and synovium inflammation were found between the late load, ALN, and load + ALN groups and the anterior cruciate ligament transection group.
CONCLUSION
Dynamic axial mechanical loading or ALN in the early stages of knee trauma protected against OA by suppressing subchondral bone remodeling. However, late loading promoted cartilage degeneration in advanced OA, indicating that reduced loading should be performed in the late stages of OA to avoid the acceleration of OA.
CLINICAL RELEVANCE
Early low-level functional exercise or antiosteoporotic drugs could clearly slow or prevent the progression of early OA. For patients with mild to severe OA, loading reduction via brace protection or maintenance of joint stability via early ligament reconstruction surgery may ameliorate OA exacerbation.
Topics: Mice; Animals; Osteophyte; X-Ray Microtomography; Cartilage, Articular; Osteoarthritis; Alendronate; Bone Remodeling; Inflammation; Disease Models, Animal
PubMed: 37103335
DOI: 10.1177/03635465231164644