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The Journal of Bone and Joint Surgery.... Dec 2019➤. Hip joint capsular ligaments (iliofemoral, ischiofemoral, and pubofemoral) play a predominant role in functional mobility and joint stability. ➤. The zona... (Review)
Review
➤. Hip joint capsular ligaments (iliofemoral, ischiofemoral, and pubofemoral) play a predominant role in functional mobility and joint stability. ➤. The zona orbicularis resists joint distraction (during neutral positions), and its aperture mechanism stabilizes the hip from adverse edge-loading (during extreme hip flexion-extension). ➤. To preserve joint function and stability, it is important to minimize capsulotomy size and avoid disrupting the zona orbicularis, preserve the femoral head size and neck length, and only repair when or as necessary without altering capsular tensions. ➤. It is not fully understood what the role of capsular tightness is in patients who have cam femoroacetabular impingement and if partial capsular release could be beneficial and/or therapeutic. ➤. During arthroplasty surgery, a femoral head implant that is nearly equivalent to the native head size with an optimal neck-length offset can optimize capsular tension and decrease dislocation risk where an intact posterior hip capsule plays a critical role in maintaining hip stability.
Topics: Arthroplasty, Replacement, Hip; Cadaver; Dissection; Female; Hip Joint; Humans; Imaging, Three-Dimensional; Joint Capsule; Joint Instability; Male; Orthopedic Procedures; Range of Motion, Articular
PubMed: 31800428
DOI: 10.2106/JBJS.19.00346 -
Best Practice & Research. Clinical... Mar 2022Rheumatoid arthritis is an autoimmune disease that causes significant morbidity. Application of cellular profiling techniques such as single-cell transcriptomics and... (Review)
Review
Rheumatoid arthritis is an autoimmune disease that causes significant morbidity. Application of cellular profiling techniques such as single-cell transcriptomics and spatial transcriptomics has uncovered novel pathogenic cell types in RA joint tissues and revealed marked heterogeneity in the cellular composition among RA patients. Together, these insights provide exciting opportunities to translate discoveries into precision medicine in RA. The present review aims to highlight novel insights into RA pathology and discuss key steps needed to translate these discoveries into actionable changes in clinical practice. We review the efforts to identify surrogate biomarkers that could be used to predict RA synovial tissue phenotypes and the corresponding responses to therapy. Finally, we discuss the opportunity to develop novel patient-derived organoid systems as a platform for therapeutic target validation.
Topics: Arthritis, Rheumatoid; Biomarkers; Humans; Precision Medicine; Synovial Membrane
PubMed: 35248489
DOI: 10.1016/j.berh.2022.101742 -
Arthritis Research & Therapy Feb 2017Modern concepts of osteoarthritis (OA) have been forever changed by modern imaging phenotypes demonstrating complex and multi-tissue pathologies involving cartilage,... (Review)
Review
Modern concepts of osteoarthritis (OA) have been forever changed by modern imaging phenotypes demonstrating complex and multi-tissue pathologies involving cartilage, subchondral bone and (increasingly recognized) inflammation of the synovium. The synovium may show significant changes, even before visible cartilage degeneration has occurred, with infiltration of mononuclear cells, thickening of the synovial lining layer and production of inflammatory cytokines. The combination of sensitive imaging modalities and tissue examination has confirmed a high prevalence of synovial inflammation in all stages of OA, with a number of studies demonstrating that synovitis is related to pain, poor function and may even be an independent driver of radiographic OA onset and structural progression. Treating key aspects of synovial inflammation therefore holds great promise for analgesia and also for structure modification. This article will review current knowledge on the prevalence of synovitis in OA and its role in symptoms and structural progression, and explore lessons learnt from targeting synovitis therapeutically.
Topics: Cartilage, Articular; Cytokines; Disease Progression; Humans; Inflammation Mediators; Knee Joint; Models, Biological; Osteoarthritis; Synovial Membrane; Synovitis
PubMed: 28148295
DOI: 10.1186/s13075-017-1229-9 -
Current Opinion in Pharmacology Dec 2022Fibroblast-like synoviocytes (FLS) are mesenchymal-derived cells that play an important role in the physiology of the synovium by producing certain components of the... (Review)
Review
Fibroblast-like synoviocytes (FLS) are mesenchymal-derived cells that play an important role in the physiology of the synovium by producing certain components of the synovial fluid and articular cartilage. In rheumatoid arthritis (RA), however, fibroblasts become a key driver of synovial inflammation and joint damage. Because of this, there has been recent interest in FLS as a therapeutic target in RA to avoid side effects such as systemic immune suppression associated with many existing RA treatments. In this review, we describe how approved treatments for RA affect FLS signaling and function and discuss the effects of investigational FLS-targeted drugs for RA.
Topics: Humans; Synoviocytes; Synovial Membrane; Arthritis, Rheumatoid; Fibroblasts; Signal Transduction
PubMed: 36228471
DOI: 10.1016/j.coph.2022.102304 -
Anatomical Science International Mar 2022Although the hip joint is regarded as inherently stable, hip pain and injuries caused by traumatic/non-traumatic hip instability are relatively common in active... (Review)
Review
Although the hip joint is regarded as inherently stable, hip pain and injuries caused by traumatic/non-traumatic hip instability are relatively common in active individuals. A comprehensive understanding of hip anatomy may provide better insight into the relationships between hip stability and clinical problems. In this review, we present our recent findings on the hip morphological characteristics, especially focusing on the intramuscular tendon of the gluteus medius tendon and its insertion sites, hip capsular attachment on the anterosuperior region of the acetabular margin, and composition of the iliofemoral ligament. We further discussed the hip stabilization mechanism based on these findings. The characteristics of the gluteus medius tendon suggest that even a single muscle has multiple functional subunits within the muscle. In addition, the characteristics of the hip capsular attachment suggest that the width of the capsular attachment is wider than previously reported, and its wide area shows adaptive morphology to mechanical stress, such as bony impression and distribution of the fibrocartilage. The composition of the iliofemoral ligament and its relation to periarticular structures suggest that some ligaments should be defined based on the pericapsular structures, such as the joint capsule, tendon, and aponeurosis, and also have the ability to dynamically coordinate joint stability. These anatomical perspectives provide a better understanding of the hip stabilization mechanism, and a biomechanical study or an in vivo imaging study, considering these perspectives, is expected in the future.
Topics: Buttocks; Hip Joint; Humans; Joint Capsule; Ligaments, Articular; Tendons
PubMed: 34686966
DOI: 10.1007/s12565-021-00638-3 -
Nature Reviews. Rheumatology Aug 2017The synovium is the major target tissue of inflammatory arthritides such as rheumatoid arthritis. The study of synovial tissue has advanced considerably throughout the... (Review)
Review
The synovium is the major target tissue of inflammatory arthritides such as rheumatoid arthritis. The study of synovial tissue has advanced considerably throughout the past few decades from arthroplasty and blind needle biopsy to the use of arthroscopic and ultrasonographic technologies that enable easier visualization and improve the reliability of synovial biopsies. Rapid progress has been made in using synovial tissue to study disease pathogenesis, to stratify patients, to discover biomarkers and novel targets, and to validate therapies, and this progress has been facilitated by increasingly diverse and sophisticated analytical and technological approaches. In this Review, we describe these approaches, and summarize how their use in synovial tissue research has improved our understanding of rheumatoid arthritis and identified candidate biomarkers that could be used in disease diagnosis and stratification, as well as in predicting disease course and treatment response.
Topics: Arthritis, Rheumatoid; Biomarkers; Biomedical Research; Humans; Synovial Fluid; Synovial Membrane
PubMed: 28701760
DOI: 10.1038/nrrheum.2017.115 -
Clinics in Geriatric Medicine May 2022Chronic pain is a substantial personal and societal burden worldwide. Osteoarthritis (OA) is one of the leading causes of chronic pain and is increasing in prevalence in... (Review)
Review
Chronic pain is a substantial personal and societal burden worldwide. Osteoarthritis (OA) is one of the leading causes of chronic pain and is increasing in prevalence in accordance with a global aging population. In addition to affecting patients' physical lives, chronic pain also adversely affects patients' mental wellbeing. However, there remain no pharmacologic interventions to slow down the progression of OA and pain-alleviating therapies are largely unsuccessful. The presence of low-level inflammation in OA has been recognized for many years as a major pathogenic driver of joint damage. Inflammatory mechanisms can occur locally in joint tissues, such as the synovium, within the sensory nervous system, as well as systemically, caused by modifiable and unmodifiable factors. Understanding how inflammation may contribute to, and modify pain in OA will be instrumental in identifying new druggable targets for analgesic therapies. In this narrative review, we discuss recent insights into inflammatory mechanisms in OA pain. We discuss how local inflammation in the joint can contribute to mechanical sensitization and to the structural neuroplasticity of joint nociceptors, through pro-inflammatory factors such as nerve growth factor, cytokines, and chemokines. We consider the role of synovitis, and the amplifying mechanisms of neuroimmune interactions. We then explore emerging evidence around the role of neuroinflammation in the dorsal root ganglia and dorsal horn. Finally, we discuss how systemic inflammation associated with obesity may modify OA pain and suggest future research directions.
Topics: Aged; Chronic Pain; Humans; Inflammation; Osteoarthritis; Synovial Membrane; Synovitis
PubMed: 35410677
DOI: 10.1016/j.cger.2021.11.013 -
Psychopharmacology Bulletin Oct 2020Adhesive capsulitis of the shoulder (AC) is characterized by fibrosis and contracture of the glenohumeral joint capsule, resulting in progressive stiffness, pain, and... (Review)
Review
BACKGROUND
Adhesive capsulitis of the shoulder (AC) is characterized by fibrosis and contracture of the glenohumeral joint capsule, resulting in progressive stiffness, pain, and restriction of motion of the shoulder. The prevalence of AC is estimated to be 2-5% of the general population. Patients with AC typically have an insidious onset of pain and can progress to severe limitation of the shoulder leading to significant disability and decreased quality of life.
OBJECTIVES
The objective of this manuscript is to provide a comprehensive review of AC with a focus on clinical presentation, natural history, pathophysiology, and various treatment modalities.
STUDY DESIGN
A review article.
SETTING
A review of literature.
METHODS
A search was made on the Pubmed database using the keywords of adhesive capsulitis, frozen shoulder, shoulder capsulitis, arthrofibrosis, shoulder pain, shoulder stiffness.
RESULTS
Our search identified numerous studies in order to provide a comprehensive review of the current understanding of the treatment and management of AC.
LIMITATIONS
There remains limited evidence in literature about the understanding of AC and optimal treatment.
CONCLUSION
AC is an important cause of chronic pain and disability. There is currently no consensus on treatment. Initial treatment modalities revolve around conservative measures as well as aggressive physical therapy. Further treatment options include intraarticular injections, hydro-dilation, nerve blocks, and for more refractory cases, surgical interventions such as arthroscopic capsulotomy.
Topics: Bursitis; Humans; Joint Capsule; Quality of Life; Shoulder Joint; Shoulder Pain
PubMed: 33633420
DOI: No ID Found -
Clinical and Translational Medicine Apr 2023Osteoarthritis (OA), a multifaceted condition, poses a significant challenge for the successful clinical development of therapeutics due to heterogeneity. However,...
BACKGROUND
Osteoarthritis (OA), a multifaceted condition, poses a significant challenge for the successful clinical development of therapeutics due to heterogeneity. However, classifying molecular endotypes of OA pathogenesis could provide invaluable phenotype-directed routes for stratifying subgroups of patients for targeted therapeutics, leading to greater chances of success in trials. This study establishes endotypes in OA soft joint tissue driven by obesity in both load-bearing and non-load bearing joints.
METHODS
Hand, hip, knee and foot joint synovial tissue was obtained from OA patients (n = 32) classified as obese (BMI > 30) or normal weight (BMI 18.5-24.9). Isolated fibroblasts (OA SF) were assayed by Olink proteomic panel, seahorse metabolic flux assay, Illumina's NextSeq 500 bulk and Chromium 10X single cell RNA-sequencing, validated by Luminex and immunofluorescence.
RESULTS
Targeted proteomic, metabolic and transcriptomic analysis found the inflammatory landscape of OA SFs are independently impacted by obesity, joint loading and anatomical site with significant heterogeneity between obese and normal weight patients, confirmed by bulk RNAseq. Further investigation by single cell RNAseq identified four functional molecular endotypes including obesity specific subsets defined by an inflammatory endotype related to immune cell regulation, fibroblast activation and inflammatory signaling, with up-regulated CXCL12, CFD and CHI3L1 expression. Luminex confirmed elevated chitase3-like-1(229.5 vs. 49.5 ng/ml, p < .05) and inhibin (20.6 vs. 63.8 pg/ml, p < .05) in obese and normal weight OA SFs, respectively. Lastly, we find SF subsets in obese patients spatially localise in sublining and lining layers of OA synovium and can be distinguished by differential expression of the transcriptional regulators MYC and FOS.
CONCLUSION
These findings demonstrate the significance of obesity in changing the inflammatory landscape of synovial fibroblasts in both load bearing and non-load bearing joints. Describing multiple heterogeneous OA SF populations characterised by specific molecular endotypes, which drive heterogeneity in OA disease pathogenesis. These molecular endotypes may provide a route for the stratification of patients in clinical trials, providing a rational for the therapeutic targeting of specific SF subsets in specific patient populations with arthritic conditions.
Topics: Humans; Proteomics; Synovial Membrane; Osteoarthritis; Obesity; Fibroblasts
PubMed: 37006170
DOI: 10.1002/ctm2.1232 -
Genome Medicine Jul 2022Synovial fibroblasts (SFs) are specialized cells of the synovium that provide nutrients and lubricants for the proper function of diarthrodial joints. Recent evidence...
BACKGROUND
Synovial fibroblasts (SFs) are specialized cells of the synovium that provide nutrients and lubricants for the proper function of diarthrodial joints. Recent evidence appreciates the contribution of SF heterogeneity in arthritic pathologies. However, the normal SF profiles and the molecular networks that govern the transition from homeostatic to arthritic SF heterogeneity remain poorly defined.
METHODS
We applied a combined analysis of single-cell (sc) transcriptomes and epigenomes (scRNA-seq and scATAC-seq) to SFs derived from naïve and hTNFtg mice (mice that overexpress human TNF, a murine model for rheumatoid arthritis), by employing the Seurat and ArchR packages. To identify the cellular differentiation lineages, we conducted velocity and trajectory analysis by combining state-of-the-art algorithms including scVelo, Slingshot, and PAGA. We integrated the transcriptomic and epigenomic data to infer gene regulatory networks using ArchR and custom-implemented algorithms. We performed a canonical correlation analysis-based integration of murine data with publicly available datasets from SFs of rheumatoid arthritis patients and sought to identify conserved gene regulatory networks by utilizing the SCENIC algorithm in the human arthritic scRNA-seq atlas.
RESULTS
By comparing SFs from healthy and hTNFtg mice, we revealed seven homeostatic and two disease-specific subsets of SFs. In healthy synovium, SFs function towards chondro- and osteogenesis, tissue repair, and immune surveillance. The development of arthritis leads to shrinkage of homeostatic SFs and favors the emergence of SF profiles marked by Dkk3 and Lrrc15 expression, functioning towards enhanced inflammatory responses and matrix catabolic processes. Lineage inference analysis indicated that specific Thy1+ SFs at the root of trajectories lead to the intermediate Thy1+/Dkk3+/Lrrc15+ SF states and culminate in a destructive and inflammatory Thy1- SF identity. We further uncovered epigenetically primed gene programs driving the expansion of these arthritic SFs, regulated by NFkB and new candidates, such as Runx1. Cross-species analysis of human/mouse arthritic SF data determined conserved regulatory and transcriptional networks.
CONCLUSIONS
We revealed a dynamic SF landscape from health to arthritis providing a functional genomic blueprint to understand the joint pathophysiology and highlight the fibroblast-oriented therapeutic targets for combating chronic inflammatory and destructive arthritic disease.
Topics: Animals; Arthritis, Rheumatoid; Fibroblasts; Humans; Inflammation; Membrane Proteins; Mice; Single-Cell Analysis; Synovial Membrane
PubMed: 35879783
DOI: 10.1186/s13073-022-01081-3