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Osteoarthritis and Cartilage Jun 2020Osteophytes are common anatomical signs of advanced osteoarthritis. It remains unclear whether they develop from physio-molecular, and/or mechanical stimuli. This study...
OBJECTIVES
Osteophytes are common anatomical signs of advanced osteoarthritis. It remains unclear whether they develop from physio-molecular, and/or mechanical stimuli. This study examined the effects of mechanical impact on the knee joint periosteum leading to osteophyte formation.
DESIGN
Eighteen mature rats received one single impact load of 53 N (30 MPa) to the periosteum of the experimental medial femoral condyles. Contralateral knees were used as controls. Animals were sacrificed at 24 h, 3, 6 and 9 weeks post-impact. Distal femurs were harvested and prepared for histology. Hematoxylin and Eosin, and Masson's trichrome stained slides were examined by light microscopy. Nuclear density was quantified to assess the tissue reaction.
RESULTS
24 h: The synovium membrane, fibrous and cambium periosteum were damaged. Blood infiltration pooled in the impacted medial collateral ligament (MCL) region. Week 3: A cartilaginous tissue spur, chondrophyte, was found in every rat at the impacted site of the MCL. Chondrophytes were composed of fibrocartilage and cartilage matrix, with signs of cartilage mineralization and remodelling activity. Week 6: Chondrophytes presented signs of more advanced mineralisation, recognized as osteophytes. Week 9: Osteophytes appeared to be more mineralized with almost no cartilage tissue.
CONCLUSIONS
Osteophytes can be induced with a single mechanical impact applied to the periosteum in rat knees. These data indicate that a moderate trauma to the periosteal layer of the joint may play a role in osteophyte development.
Topics: Animals; Disease Models, Animal; Hindlimb; Joints; Mechanical Phenomena; Osteophyte; Rats; Rats, Sprague-Dawley
PubMed: 32147535
DOI: 10.1016/j.joca.2020.02.834 -
Piezo1 expression in chondrocytes controls endochondral ossification and osteoarthritis development.Bone Research Feb 2024Piezo proteins are mechanically activated ion channels, which are required for mechanosensing functions in a variety of cell types. While we and others have previously...
Piezo proteins are mechanically activated ion channels, which are required for mechanosensing functions in a variety of cell types. While we and others have previously demonstrated that the expression of Piezo1 in osteoblast lineage cells is essential for bone-anabolic processes, there was only suggestive evidence indicating a role of Piezo1 and/or Piezo2 in cartilage. Here we addressed the question if and how chondrocyte expression of the mechanosensitive proteins Piezo1 or Piezo2 controls physiological endochondral ossification and pathological osteoarthritis (OA) development. Mice with chondrocyte-specific inactivation of Piezo1 (Piezo1), but not of Piezo2, developed a near absence of trabecular bone below the chondrogenic growth plate postnatally. Moreover, all Piezo1 animals displayed multiple fractures of rib bones at 7 days of age, which were located close to the growth plates. While skeletal growth was only mildly affected in these mice, OA pathologies were markedly less pronounced compared to littermate controls at 60 weeks of age. Likewise, when OA was induced by anterior cruciate ligament transection, only the chondrocyte inactivation of Piezo1, not of Piezo2, resulted in attenuated articular cartilage degeneration. Importantly, osteophyte formation and maturation were also reduced in Piezo1 mice. We further observed increased Piezo1 protein abundance in cartilaginous zones of human osteophytes. Finally, we identified Ptgs2 and Ccn2 as potentially relevant Piezo1 downstream genes in chondrocytes. Collectively, our data do not only demonstrate that Piezo1 is a critical regulator of physiological and pathological endochondral ossification processes, but also suggest that Piezo1 antagonists may be established as a novel approach to limit osteophyte formation in OA.
Topics: Animals; Humans; Mice; Cartilage, Articular; Chondrocytes; Ion Channels; Osteoarthritis; Osteogenesis; Osteophyte
PubMed: 38395992
DOI: 10.1038/s41413-024-00315-x -
Osteoarthritis and Cartilage Dec 2015To develop a radiographic atlas of osteoarthritis (OA) for use as a template and guide for standardized scoring of radiographic features of OA of the ankle and hindfoot... (Review)
Review
OBJECTIVE
To develop a radiographic atlas of osteoarthritis (OA) for use as a template and guide for standardized scoring of radiographic features of OA of the ankle and hindfoot joints.
METHOD
Under Institutional Review Board approval, ankle and hindfoot images were selected from a cohort study and from among cases that underwent ankle radiography during a 6-month period at Duke University Medical Center. Missing OA pathology was obtained through supplementation of cases with the assistance of a foot and ankle specialist in Orthopaedic surgery and a musculoskeletal radiologist. Images were obtained and reviewed without patient identifying information. Images went through multiple rounds of review and final images were selected by consensus of the study team. For intra-rater and inter-rater reliability, the kappa statistic was calculated for two readings by three musculoskeletal radiologists, a minimum of two weeks apart, of ankle and hindfoot radiographs from 30 anonymized subjects.
RESULTS
The atlas demonstrates individual radiographic features (osteophyte and joint space narrowing (JSN)) and Kellgren-Lawrence grade for all aspects of the talocrural (ankle joint proper) and talocalcaneal (subtalar) joints. Reliability of scoring based on the atlas was quite good to excellent for most features indicated. Additional examples of ankle joint findings are illustrated including sclerosis, os trigonum, subchondral cysts and talar tilt.
CONCLUSIONS
It is anticipated that this atlas will assist with standardization of scoring of ankle and hindfoot OA by basic and clinical OA researchers.
Topics: Ankle Joint; Atlases as Topic; Cohort Studies; Foot Joints; Humans; Observer Variation; Osteoarthritis; Osteophyte; Radiography; Reproducibility of Results; Subtalar Joint; Talus
PubMed: 26318654
DOI: 10.1016/j.joca.2015.08.008 -
Orthopaedic Surgery Jul 2023Finding reliable tools to predict alignment change after medial mobile-bearing unicompartmental knee arthroplasty (UKA) can help surgeons avoid under- or...
OBJECTIVE
Finding reliable tools to predict alignment change after medial mobile-bearing unicompartmental knee arthroplasty (UKA) can help surgeons avoid under- or over-correction. This prospective study aimed to investigate whether the parameters related to medial collateral ligament tension on valgus stress radiograph can predict the alignment change of medial mobile-bearing UKA and establish a prediction model.
METHODS
This study prospectively included the patients undergoing medial mobile-bearing UKA for knee osteoarthritis from November 2018 and April 2021. Patients took valgus stress radiograph and MRI preoperatively and took full-length weight-bearing anterior-posterior radiograph of the lower extremity preoperatively and postoperatively. The medial joint space width (MJSW) on valgus stress radiograph, area of femoral and tibial osteophyte on MRI, medial extrusion distance (MED) of the meniscus on MRI, and the change in hip-knee-ankle angle (∆HKAA) were measured. Factors influencing ∆HKAA were analyzed by correlation analysis. Univariable and multivariable linear regression analysis was performed to establish a prediction model of ∆HKAA.
RESULTS
One hundred and seven knees were included. On average, the preoperative HKAA was 170.84° ± 3.73°, and UKA corrected the alignment to 175.16° ± 3.21° postoperatively (p < 0.001), with ∆HKAA of 4.33° ± 1.93°. Correlation analysis showed that ∆HKAA correlated with MJSW (r = 0.628, p < 0.001), MED (r = 0.262, p < 0.001), and tibial osteophyte area (r = 0.235, p < 0.001). The prediction model for ∆HKAA was obtained by multivariable linear regression: ∆HKAA = -2.003 + 0.947 × MJSW(mm) + 1.838 × total osteophyte area(cm ).
CONCLUSION
Valgus stress radiographic MJSW and osteophyte area are correlated to the alignment change of medial mobile-bearing UKA. The prediction model for HKAA change is: ∆HKAA = -2.003 + 0.947 × MJSW(mm) + 1.838 × total osteophyte area(cm ).
Topics: Humans; Arthroplasty, Replacement, Knee; Osteophyte; Prospective Studies; Knee Joint; Osteoarthritis, Knee; Knee Prosthesis; Retrospective Studies
PubMed: 37395116
DOI: 10.1111/os.13823 -
Journal of Orthopaedic Surgery (Hong... 2021To summarize the current evidence on surgical treatment for large bridging osteophytes of the anterior cervical spine from Diffuse Idiopathic Skeletal Hyperostosis... (Review)
Review
To summarize the current evidence on surgical treatment for large bridging osteophytes of the anterior cervical spine from Diffuse Idiopathic Skeletal Hyperostosis (DISH). In the current review, the surgical treatment of secondary dysphagia from DISH was the most useful treatment. We propose a treatment algorithm for management of this condition because currently there are only case reports and retrospective studies available. Literature search was performed using the MeSH terms "Anterior Cervical Osteophyte," "Diffuse Idiopathic Skeletal Hyperostosis (DISH)," and "Dysphagia" and "Treatment" for articles published between January 2000 and February 2020. PubMed search identified 117 articles that met the initial screening criteria. Detailed analysis identified the 40 best matching articles, following which the full inclusion and exclusion criteria left 11 articles for this review. Incidence of secondary dysphagia was associated with DISH in elderly patients (average 65 years). The major clinical findings were dysphagia or respiratory compromise, with the most common level of bridging osteophytes of the cervical spine at C3-C5. There were 10 articles on surgical treatment involving anterior cervical osteophytectomy without fusion, 1 for multilevel cervical oblique corpectomy, 1 for anterior cervical discectomy with fusion plus plate, and 1 for anterior cervical osteophytectomy with stand-alone PEEK cage or plus plate. All the cases resulted in significant improvement without recurrence, with only 1 case having post-operative complications. Follow-up duration was 3-70.3 months. Surgical intervention for anterior cervical osteophytectomy appears to result in improved outcomes. However, there could be disadvantages concerning cervical spine motion if cervical osteophytectomy with cervical discectomy and fusion (ACDF) plus plate system is done.
Topics: Aged; Cervical Vertebrae; Deglutition Disorders; Humans; Hyperostosis, Diffuse Idiopathic Skeletal; Osteophyte; Retrospective Studies
PubMed: 34592856
DOI: 10.1177/23094990211041783 -
The American Journal of Pathology Jan 2024Osteophytes in osteoarthritis (OA) joints contribute to restriction of joint movement, joint pain, and OA progression, but little is known about osteophyte regulators....
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.
Topics: Humans; Cartilage, Articular; Chondrocytes; Intercellular Signaling Peptides and Proteins; Interleukin-6; Knee Joint; Osteoarthritis; Osteoarthritis, Knee; Osteophyte
PubMed: 37918800
DOI: 10.1016/j.ajpath.2023.10.005 -
Reumatologia Clinica Nov 2021
Topics: Cervical Vertebrae; Deglutition Disorders; Humans; Osteophyte
PubMed: 34756319
DOI: 10.1016/j.reumae.2020.09.005 -
Journal of Orthopaedic Research :... Feb 2018Osteophytes are a typical radiographic finding during osteoarthritis (OA), but the mechanisms leading to their formation are not well known. Comparatively, fracture... (Comparative Study)
Comparative Study
Osteophytes are a typical radiographic finding during osteoarthritis (OA), but the mechanisms leading to their formation are not well known. Comparatively, fracture calluses have been studied extensively; therefore, drawing comparisons between osteophytes and fracture calluses may lead to a deeper understanding of osteophyte formation. In this study, we compared the time courses of osteophyte and fracture callus formation, and investigated mechanisms contributing to development of these structure. Additionally, we investigated the effect of mechanical unloading on the formation of both fracture calluses and osteophytes. Mice underwent either transverse femoral fracture or non-invasive anterior cruciate ligament rupture. Fracture callus and osteophyte size and ossification were evaluated after 3, 5, 7, 14, 21, or 28 days. Additional mice were subjected to hindlimb unloading after injury for 3, 7, or 14 days. Protease activity and gene expression profiles after injury were evaluated after 3 or 7 days of normal ambulation or hindlimb unloading using in vivo fluorescence reflectance imaging (FRI) and quantitative PCR. We found that fracture callus and osteophyte growth achieved similar developmental milestones, but fracture calluses formed and ossified at earlier time points. Hindlimb unloading ultimately led to a threefold decrease in chondro/osteophyte area, and a twofold decrease in fracture callus area. Unloading was also associated with decreased inflammation and protease activity in injured limbs detected with FRI, particularly following ACL rupture. qPCR analysis revealed disparate cellular responses in fractured femurs and injured joints, suggesting that fracture calluses and osteophytes may form via different inflammatory, anabolic, and catabolic pathways. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:699-710, 2018.
Topics: Animals; Anterior Cruciate Ligament Injuries; Biomechanical Phenomena; Bone and Bones; Bony Callus; Female; Femoral Fractures; Fracture Healing; Gene Expression; Mice, Inbred C57BL; Osteogenesis; Osteophyte; Peptide Hydrolases; X-Ray Microtomography
PubMed: 29058776
DOI: 10.1002/jor.23779 -
Bone Dec 2021It remains unclear how the different features of radiographic hip osteoarthritis (rHOA) contribute to hip pain. We examined the relationship between rHOA, including its...
OBJECTIVE
It remains unclear how the different features of radiographic hip osteoarthritis (rHOA) contribute to hip pain. We examined the relationship between rHOA, including its individual components, and hip pain using a novel dual-energy x-ray absorptiometry (DXA)-based method.
METHODS
Hip DXAs were obtained from UK Biobank. A novel automated method obtained minimum joint space width (mJSW) from points placed around the femoral head and acetabulum. Osteophyte areas at the lateral acetabulum, superior and inferior femoral head were derived manually. Semi-quantitative measures of osteophytes and joint space narrowing (JSN) were combined to define rHOA. Logistic regression was used to examine the relationships between these variables and hip pain, obtained via questionnaires.
RESULTS
6807 hip DXAs were examined. rHOA was present in 353 (5.2%) individuals and was associated with hip pain [OR 2.42 (1.78-3.29)] and hospital diagnosed OA [6.01 (2.98-12.16)]. Total osteophyte area but not mJSW was associated with hip pain in mutually adjusted models [1.31 (1.23-1.39), 0.95 (0.87-1.04) respectively]. On the other hand, JSN as a categorical variable showed weak associations between grade ≥ 1 and grade ≥ 2 JSN with hip pain [1.30 (1.06-1.60), 1.80 (1.34-2.42) respectively]. Acetabular, superior and inferior femoral osteophyte areas were all independently associated with hip pain [1.13 (1.06-1.20), 1.13 (1.05-1.24), 1.10 (1.03-1.17) respectively].
CONCLUSION
In this cohort, the relationship between rHOA and prevalent hip pain was explained by 2-dimensional osteophyte area, but not by the apparent mJSW. Osteophytes at different locations showed important, potentially independent, associations with hip pain, possibly reflecting the contribution of distinct biomechanical pathways.
Topics: Absorptiometry, Photon; Biological Specimen Banks; Cross-Sectional Studies; Humans; Osteoarthritis, Hip; Osteophyte; Pain; Radiography; United Kingdom
PubMed: 34389476
DOI: 10.1016/j.bone.2021.116146 -
Osteoarthritis and Cartilage Jan 2017Osteoarthritis (OA) is a heterogeneous, multi-tissue disease. We hypothesised that different histopathological features characterise different stages during knee OA...
OBJECTIVE
Osteoarthritis (OA) is a heterogeneous, multi-tissue disease. We hypothesised that different histopathological features characterise different stages during knee OA progression, and that discrete subgroups can be defined based on validated measures of OA histopathological features.
DESIGN
Medial tibial plateaux and synovium were from 343 post-mortem (PM) and 143 OA arthroplasty donations. A 'chondropathy/osteophyte' group (n = 217) was classified as PM cases with osteophytes or macroscopic medial tibiofemoral chondropathy lesions ≥grade 3 to represent pre-surgical (early) OA. 'Non-arthritic' controls (n = 48) were identified from the remaining PM cases. Mankin histopathological scores were subjected to Rasch analysis and supplemented with histopathological scores for subchondral bone marrow replacement and synovitis. Item weightings were derived by principle components analysis (PCA). Histopathological subgroups were sought using latent class analysis (LCA).
RESULTS
Chondropathy, synovitis and osteochondral pathology were each associated with OA at arthroplasty, but each was also identified in some 'non-arthritic' controls. Tidemark breaching in the chondropathy/osteophyte group was greater than in non-arthritic controls. Three histopathological subgroups were identified, characterised as 'mild OA', or 'severe OA' with mild or moderate/severe synovitis.
CONCLUSIONS
Presence and severity of synovitis helps define distinct histopathological OA subgroups. The absence of a discrete 'normal' subgroup indicates a pathological continuum between normality and OA status. Identifying specific pathological processes and their clinical correlates in OA subgroups has potential to accelerate the development of more effective therapies.
Topics: Adult; Aged; Chondrocytes; Disease Progression; Female; Humans; Knee Joint; Male; Middle Aged; Osteoarthritis, Knee; Osteophyte; Severity of Illness Index; Synovitis
PubMed: 27720884
DOI: 10.1016/j.joca.2016.09.021