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International Journal of Infectious... Apr 2019Treatment of bone and joint infections can be challenging as antibiotics should penetrate through the rigid bone structure and into the synovial space. Several... (Review)
Review
Treatment of bone and joint infections can be challenging as antibiotics should penetrate through the rigid bone structure and into the synovial space. Several pharmacokinetic studies measured the extent of penetration of different antibiotics into bone and joint tissues. This review discusses the results of these studies and compares them with minimum inhibitory concentrations (MIC) of common pathogens implicated in bone and joint infections in order to determine which antibiotics may have a greater potential in the treatment of such infections. Clinical outcomes were also evaluated as data were available. More than 30 antibiotics were evaluated. Overall, most antibiotics, including amoxicillin, piperacillin/tazobactam, cloxacillin, cephalosporins, carbapenems, aztreonam, aminoglycosides, fluoroquinolones, doxycycline, vancomycin, linezolid, daptomycin, clindamycin, trimethoprim/sulfamethoxazole, fosfomycin, rifampin, dalbavancin, and oritavancin, showed good penetration into bone and joint tissues reaching concentrations exceeding the MIC and/or MIC breakpoints of common bone and joint infections pathogens. Few exceptions include penicillin and metronidazole which showed a lower than optimum penetration into bones, and the latter as well as flucloxacillin had poor profiles in terms of joint space penetration. Of note, studies on joint space penetration were fewer than studies on bone tissue penetration. Although clinical studies in osteomyelitis and septic arthritis are not available for all of the evaluated antibiotics, these pharmacokinetic results indicate that agents with good penetration profiles would have a potential utilization in such infections.
Topics: Anti-Bacterial Agents; Arthritis, Infectious; Bone and Bones; Humans; Joints; Osteomyelitis
PubMed: 30772469
DOI: 10.1016/j.ijid.2019.02.005 -
Annals of the Rheumatic Diseases Mar 2023Fibroblasts in synovium include fibroblast-like synoviocytes (FLS) in the lining and + connective-tissue fibroblasts in the sublining. We aimed to investigate their...
OBJECTIVES
Fibroblasts in synovium include fibroblast-like synoviocytes (FLS) in the lining and + connective-tissue fibroblasts in the sublining. We aimed to investigate their developmental origin and relationship with adult progenitors.
METHODS
To discriminate between -lineage cells deriving from the embryonic joint interzone and other -expressing fibroblasts and progenitors, adult mice were used and cartilage injury was induced to activate progenitors. Cells were isolated from knees, fibroblasts and progenitors were sorted by fluorescence-activated cell-sorting based on developmental origin, and analysed by single-cell RNA-sequencing. Flow cytometry and immunohistochemistry were used for validation. Clonal-lineage mapping was performed using mice.
RESULTS
In steady state, + sublining fibroblasts were of mixed ontogeny. In contrast, + lining fibroblasts predominantly derived from the embryonic joint interzone and included -expressing progenitors distinct from molecularly defined FLS. Clonal-lineage tracing revealed compartmentalisation of -lineage fibroblasts between lining and sublining. Following injury, lining hyperplasia resulted from proliferation and differentiation of -expressing progenitors, with additional recruitment of non--lineage cells, into FLS. Consistent with this, a second population of proliferating cells, enriched near blood vessels in the sublining, supplied activated multipotent cells predicted to give rise to + fibroblasts, and to feed into the FLS differentiation trajectory. Transcriptional programmes regulating fibroblast differentiation trajectories were uncovered, identifying Sox5 and Foxo1 as key FLS transcription factors in mice and humans.
CONCLUSIONS
Our findings blueprint a cell atlas of mouse synovial fibroblasts and progenitors in healthy and injured knees, and provide novel insights into the cellular and molecular principles governing the organisation and maintenance of adult synovial joints.
Topics: Humans; Adult; Mice; Animals; Receptor, Platelet-Derived Growth Factor alpha; Joints; Synovial Membrane; Synoviocytes; Fibroblasts
PubMed: 36414376
DOI: 10.1136/ard-2021-221682 -
Nature Communications Apr 2021Insufficient apoptosis of inflammatory macrophages and osteoclasts (OCs) in rheumatoid arthritis (RA) joints contributes toward the persistent progression of joint...
Insufficient apoptosis of inflammatory macrophages and osteoclasts (OCs) in rheumatoid arthritis (RA) joints contributes toward the persistent progression of joint inflammation and destruction. Here, we deliver celastrol (CEL) to selectively induce apoptosis of OCs and macrophages in arthritic joints, with enzyme-responsive nanoparticles (termed PRNPs) composed of RGD modified nanoparticles (termed RNPs) covered with cleavable PEG chains. CEL-loaded PRNPs (CEL-PRNPs) dually target OCs and inflammatory macrophages derived from patients with RA via an RGD-αvβ3 integrin interaction after PEG cleavage by matrix metalloprotease 9, leading to increased apoptosis of these cells. In an adjuvant-induced arthritis rat model, PRNPs have an arthritic joint-specific distribution and CEL-PRNPs efficiently reduce the number of OCs and inflammatory macrophages within these joints. Additionally, rats with advanced arthritis go into inflammatory remission with bone erosion repair and negligible side effects after CEL-PRNPs treatment. These findings indicate potential for targeting chemotherapy-induced apoptosis in the treatment of advanced inflammatory arthritis.
Topics: Animals; Apoptosis; Arthritis, Rheumatoid; Bone and Bones; Endocytosis; Female; Human Umbilical Vein Endothelial Cells; Humans; Inflammation; Joints; Lipopolysaccharides; Macrophages; Mice, Inbred C57BL; Nanoparticles; Oligopeptides; Osteoclasts; Pentacyclic Triterpenes; Rats; Synovial Membrane; Tissue Distribution; Triterpenes; X-Ray Microtomography; Mice
PubMed: 33846342
DOI: 10.1038/s41467-021-22454-z -
The Kaohsiung Journal of Medical... Apr 2018Temporomandibular joint (TMJ) is one of the most complex joints of the human body. Due to its unique movement, in terms of combination of rotation and translator... (Review)
Review
Temporomandibular joint (TMJ) is one of the most complex joints of the human body. Due to its unique movement, in terms of combination of rotation and translator movement, disc of the joint plays an important role to maintain its normal function. In order to sustain the normal function of the TMJ, disc must be kept in proper position as well as maintain normal shape in all circumstances. Once the disc is not any more in its normal position during function of the joint, disturbance of the joint can be occurred which will lead to subsequent distortion of the disc. Shape of the disc can be influenced by many factors i.e.: abnormal function or composition of the disc itself. Etiology of the internal derangement of the disc remains controversial. Multifactorial theory has been postulated in most of previous manuscripts. Disc is composed of mainly extracellular matrix. Abnormal proportion of collagen type I & III may also leads to joint hypermobility which may be also a predisposing factor of this disorder. Thus it can be recognized as local manifestation of a systemic disorder. Different treatment modalities with from conservative treatment to surgical intervention distinct success rate have been reported. Recently treatment with extracellular matrix injection becomes more and more popular to strengthen the joint itself. Since multifactorial in character, the best solution of the treatment modalities should be aimed to resolve possible etiology from different aspects. Team work may be indication to reach satisfied results.
Topics: Arthrocentesis; Arthroscopy; Collagen Type I; Collagen Type III; Extracellular Matrix; Humans; Hyaluronic Acid; Orthopedic Equipment; Physical Therapy Modalities; Synovial Fluid; Temporomandibular Joint; Temporomandibular Joint Disorders
PubMed: 29655411
DOI: 10.1016/j.kjms.2018.01.004 -
Developmental Dynamics : An Official... Apr 2017Here we review studies identifying regulatory networks responsible for synovial, cartilaginous, and fibrous joint development. Synovial joints, characterized by the... (Review)
Review
Here we review studies identifying regulatory networks responsible for synovial, cartilaginous, and fibrous joint development. Synovial joints, characterized by the fluid-filled synovial space between the bones, are found in high-mobility regions and are the most common type of joint. Cartilaginous joints such as the intervertebral disc unite adjacent bones through either a hyaline cartilage or a fibrocartilage intermediate. Fibrous joints, which include the cranial sutures, form a direct union between bones through fibrous connective tissue. We describe how the distinct morphologic and histogenic characteristics of these joint classes are established during embryonic development. Collectively, these studies reveal that despite the heterogeneity of joint strength and mobility, joint development throughout the skeleton utilizes common signaling networks via long-range morphogen gradients and direct cell-cell contact. This suggests that different joint types represent specialized variants of homologous developmental modules. Identifying the unifying aspects of the signaling networks between joint classes allows a more complete understanding of the signaling code for joint formation, which is critical to improving strategies for joint regeneration and repair. Developmental Dynamics 246:262-274, 2017. © 2016 Wiley Periodicals, Inc.
Topics: Animals; Cartilage, Articular; Gene Regulatory Networks; Humans; Joint Capsule; Joints; Morphogenesis; Regeneration; Signal Transduction
PubMed: 27859991
DOI: 10.1002/dvdy.24472 -
Frontiers in Endocrinology 2023Osteoarthritis (OA) is a disabling disease with significant morbidity worldwide. OA attacks the large synovial joint, including the peripheral joints and... (Review)
Review
Osteoarthritis (OA) is a disabling disease with significant morbidity worldwide. OA attacks the large synovial joint, including the peripheral joints and temporomandibular joint (TMJ). As a representative of peripheral joint OA, knee OA shares similar symptoms with TMJ OA. However, these two joints also display differences based on their distinct development, anatomy, and physiology. Extracellular vesicles (EVs) are phospholipid bilayer nanoparticles, including exosomes, microvesicles, and apoptotic bodies. EVs contain proteins, lipids, DNA, micro-RNA, and mRNA that regulate tissue homeostasis and cell-to-cell communication, which play an essential role in the progression and treatment of OA. They are likely to partake in mechanical response, extracellular matrix degradation, and inflammatory regulation during OA. More evidence has shown that synovial fluid and synovium-derived EVs may serve as OA biomarkers. More importantly, mesenchymal stem cell-derived EV shows a therapeutic effect on OA. However, the different function of EVs in these two joints is largely unknown based on their distinct biological characteristic. Here, we reviewed the effects of EVs in OA progression and compared the difference between the knee joint and TMJ, and summarized their potential therapeutic role in the treatment of OA.
Topics: Humans; Osteoarthritis; Temporomandibular Joint; Extracellular Vesicles; Synovial Membrane; Synovial Fluid
PubMed: 36950682
DOI: 10.3389/fendo.2023.1158744 -
Frontiers in Immunology 2022Inflammatory arthritis is an inflammatory disease that involves the joints and surrounding tissues. Synovial hyperplasia often presents when joints become inflamed due...
Inflammatory arthritis is an inflammatory disease that involves the joints and surrounding tissues. Synovial hyperplasia often presents when joints become inflamed due to immune cell infiltration. Synovial membrane is an important as well as a highly specific component of the joint, and its lesions can lead to degeneration of the joint surface, causing pain and joint disability or affecting the patients' quality of life in severe cases. Synovial macrophages (SMs) are one of the cellular components of the synovial membrane, which not only retain the function of macrophages to engulf foreign bodies in the joint cavity, but also interact with synovial fibroblasts (SFs), T cells, B cells, and other inflammatory cells to promote the production of a variety of pro-inflammatory cytokines and chemokines, such as TNF-α, IL-1β, IL-8, and IL-6, which are involved in the pathogenic process of inflammatory arthritis. SMs from different tissue sources have differently differentiated potentials and functional expressions. This article provides a summary on studies pertaining to SMs in inflammatory arthritis, and explores their role in its treatment, in order to highlight novel treatment modalities for the disease.
Topics: Arthritis, Rheumatoid; Humans; Joints; Macrophages; Quality of Life; Synovial Membrane
PubMed: 35958604
DOI: 10.3389/fimmu.2022.905356 -
Osteoarthritis and Cartilage May 2021Osteoarthritis (OA) poses a major health and economic burden worldwide due to an increasing number of patients and the unavailability of disease-modifying drugs. In this... (Review)
Review
Osteoarthritis (OA) poses a major health and economic burden worldwide due to an increasing number of patients and the unavailability of disease-modifying drugs. In this review, the latest understanding of the involvement of the cholinergic system in joint homeostasis and OA will be outlined. First of all, the current evidence on the presence of the cholinergic system in the normal and OA joint will be described. Cholinergic innervation as well as the non-neuronal cholinergic system are detected. In a variety of inflammatory diseases, the classic cholinergic anti-inflammatory pathway lately received a lot of attention as via this pathway cholinergic agonists can reduce inflammation. The role of this cholinergic anti-inflammatory pathway in the context of OA will be discussed. Activation of this pathway improved the progression of the disease. Secondly, chondrocyte hypertrophy plays a pivotal role in osteophyte formation and OA development; the impact of the cholinergic system on hypertrophic chondroblasts and endochondral ossification will be evaluated. Cholinergic stimulation increased chondrocyte proliferation, delayed chondrocyte differentiation and caused early mineralisation. Moreover, acetylcholinesterase and butyrylcholinesterase affect the endochondral ossification via an acetylcholine-independent pathway. Thirdly, subchondral bone is critical for cartilage homeostasis and metabolism; the cholinergic system in subchondral bone homeostasis and disorders will be explored. An increase in osteoblast proliferation and osteoclast apoptosis is observed. Lastly, current therapeutic strategies for OA are limited to symptom relief; here the impact of smoking on disease progression and the potential of acetylcholinesterase inhibitors as candidate disease-modifying drug for OA will be discussed.
Topics: Acetylcholine; Bone Cysts; Cartilage, Articular; Cholinergic Neurons; Cholinesterase Inhibitors; Chondrocytes; Disease Progression; Humans; Hypertrophy; Inflammation; Joints; Osteoarthritis; Sclerosis; Smoking; Synovial Membrane; Synovitis
PubMed: 33609692
DOI: 10.1016/j.joca.2021.02.005 -
Seminars in Cell & Developmental Biology Feb 2017Within each synovial joint, the articular cartilage is uniquely adapted to bear dynamic compressive loads and shear forces throughout the joint's range of motion. Injury... (Review)
Review
Within each synovial joint, the articular cartilage is uniquely adapted to bear dynamic compressive loads and shear forces throughout the joint's range of motion. Injury and age-related degeneration of the articular cartilage often lead to significant pain and disability, as the intrinsic repair capability of the tissue is extremely limited. Current surgical and biological treatment options have been unable to restore cartilage de novo. Before successful clinical cartilage restoration strategies can be developed, a better understanding of how the cartilage forms during normal development is essential. This review focuses on recent progress made towards addressing key questions about articular cartilage morphogenesis, including the origin of synovial joint progenitor cells, postnatal development and growth of the tissue. These advances have provided novel insight into fundamental questions about the developmental biology of articular cartilage, as well as potential cell sources that may participate in joint response to injury.
Topics: Aging; Animals; Cartilage, Articular; Embryonic Development; Humans; Joints; Morphogenesis; Stem Cells
PubMed: 27771363
DOI: 10.1016/j.semcdb.2016.10.005 -
Current Osteoporosis Reports Feb 2015Synovial joint morphogenesis occurs through the condensation of mesenchymal cells into a non-cartilaginous region known as the interzone and the specification of... (Review)
Review
Synovial joint morphogenesis occurs through the condensation of mesenchymal cells into a non-cartilaginous region known as the interzone and the specification of progenitor cells that commit to the articular fate. Although several signaling molecules are expressed by the interzone, the mechanism is poorly understood. For treatments of cartilage injuries, it is critical to discover the presence of joint progenitor cells in adult tissues and their expression gene pattern. Potential stem cell niches have been found in different joint regions, such as the surface zone of articular cartilage, synovium, and groove of Ranvier. Inherited joint malformations as well as joint-degenerating conditions are often associated with other skeletal defects and may be seen as the failure of morphogenic factors to establish the correct microenvironment in cartilage and bone. Therefore, exploring how joints form can help us understand how cartilage and bone are damaged and develop drugs to reactivate this developing mechanism.
Topics: Homeostasis; Humans; Joints; Morphogenesis; Organogenesis
PubMed: 25431159
DOI: 10.1007/s11914-014-0247-7