scholarly journals Monocytes, Macrophages, and Their Potential Niches in Synovial Joints – Therapeutic Targets in Post-Traumatic Osteoarthritis?

2021 ◽  
Vol 12 ◽  
Author(s):  
Patrick Haubruck ◽  
Marlene Magalhaes Pinto ◽  
Babak Moradi ◽  
Christopher B. Little ◽  
Rebecca Gentek
Keyword(s):  
Synovial Fibroblasts ◽  
Cellular Interactions ◽  
Joint Injury ◽  
Synovial Joints ◽  
Joint Disorder ◽  
Hematopoietic Stroma ◽  
Post Traumatic ◽  
Micro Anatomy ◽  
Molecular Signals ◽  
Potential Interactions

Synovial joints are complex structures that enable normal locomotion. Following injury, they undergo a series of changes, including a prevalent inflammatory response. This increases the risk for development of osteoarthritis (OA), the most common joint disorder. In healthy joints, macrophages are the predominant immune cells. They regulate bone turnover, constantly scavenge debris from the joint cavity and, together with synovial fibroblasts, form a protective barrier. Macrophages thus work in concert with the non-hematopoietic stroma. In turn, the stroma provides a scaffold as well as molecular signals for macrophage survival and functional imprinting: “a macrophage niche”. These intricate cellular interactions are susceptible to perturbations like those induced by joint injury. With this review, we explore how the concepts of local tissue niches apply to synovial joints. We introduce the joint micro-anatomy and cellular players, and discuss their potential interactions in healthy joints, with an emphasis on molecular cues underlying their crosstalk and relevance to joint functionality. We then consider how these interactions are perturbed by joint injury and how they may contribute to OA pathogenesis. We conclude by discussing how understanding these changes might help identify novel therapeutic avenues with the potential of restoring joint function and reducing post-traumatic OA risk.

The Cervical Synovial Joints as Sources of Post-Traumatic Headache

1996 ◽  
Vol 4 (4) ◽  
pp. 81-94 ◽  
Author(s):  
Susan M. Lord ◽  
Nikolai Bogduk
Keyword(s):  
Synovial Joints ◽  
Post Traumatic

scholarly journals Inhibition of Early Response Genes Prevents Changes in Global Joint Metabolomic Profiles in Mouse Post-Traumatic Osteoarthritis

2018 ◽  
Author(s):  
Dominik R. Haudenschild ◽  
Alyssa K. Carlson ◽  
Donald L. Zignego ◽  
Jasper H.N. Yik ◽  
Jonathan K. Hilmer ◽  
...  
Keyword(s):  
Transcriptional Activation ◽  
Cellular Responses ◽  
Early Response ◽  
Primary Response ◽  
Response Gene ◽  
Joint Injury ◽  
Non Invasive ◽  
Primary Response Gene ◽  
Post Traumatic ◽  
Early Response Genes

Osteoarthritis (OA) is the most common degenerative joint disease, and joint injury increases the risk of OA by 10-fold. Although the injury event itself damages joint tissues, a substantial amount of secondary damage is mediated by the cellular responses to the injury. Cellular responses include the production and activation of proteases (MMPs, ADAMTSs, Cathepsins), the production of inflammatory cytokines, and we hypothesize, changes to the joint metabolome. The trajectory of cellular responses is driven by the transcriptional activation of early response genes, which requires Cdk9-dependent RNA Polymerase II phosphorylation. Flavopiridol is a potent and selective inhibitor of Cdk9 kinase activity, which prevents the transcriptional activation of early response genes. To model post-traumatic osteoarthritis, we subjected mice to non-invasive ACL-rupture joint injury. Following injury, mice were treated with flavopiridol to inhibit Cdk9-dependent transcriptional activation, or vehicle control. Global joint metabolomics were analyzed 1 hour after injury. We found that injury induced metabolomic changes, including increases in Vitamin D3 metabolism and others. Importantly, we found that inhibition of primary response gene activation at the time of injury largely prevented the global changes in the metabolomics profiles. Cluster analysis of joint metabolomes identified groups of injury-induced and drug-responsive metabolites, which may offer novel targets for cell-mediated secondary joint damage. Metabolomic profiling provides an instantaneous snapshot of biochemical activity representing cellular responses, and these data demonstrate the potential for inhibition of early response genes to alter the trajectory of cell-mediated degenerative changes following joint injury.Significance StatementJoint injury is an excellent predictor of future osteoarthritis. It is increasingly apparent that the acute cellular responses to injury contribute to the initiation and pathogenesis of OA. Although changes to the joint transcriptome have been extensively studied in the context of joint injury, little is known about changes to small-molecule metabolites. Here we use a non-invasive ACL rupture model of joint injury in mice to identify injury-induced changes to the global metabolomic profiles. In one experimental group we prevented the activation of primary response gene transcription using the Cdk9 inhibitor flavopiridol. Through this comparison, we identified two sets of metabolites that change acutely after joint injury: those that require transcription of primary response genes, and those that do not.

scholarly journals Loss of α2-6 sialylation promotes the transformation of synovial fibroblasts into a pro-inflammatory phenotype in Rheumatoid Arthritis

2020 ◽  
Author(s):  
Yilin Wang ◽  
Aneesah Khan ◽  
Aristotelis Antonopoulos ◽  
Laura Bouché ◽  
Christopher D Buckley ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Immune Cells ◽  
Joint Destruction ◽  
Inflammatory Cells ◽  
Synovial Fibroblasts ◽  
Surface Proteins ◽  
Cellular Interactions ◽  
Inflammatory Microenvironment ◽  
Distinct Disease ◽  
Inflammatory Phenotype

AbstractIn healthy joints, synovial fibroblasts (SFs) provide the microenvironment required to mediate homeostasis but are recognized to adopt a pathological role in rheumatoid arthritis (RA), promoting the infiltration and activation of immune cells to perpetuate local inflammation, pain and joint destruction. Carbohydrates (glycans) attached to cell surface proteins are fundamental regulators of cellular interactions between stromal and immune cells, but very little is known about the glycome of SFs or how glycosylation regulates their biology. Here we fill these gaps in our understanding of stromal guided pathophysiology by systematically mapping glycosylation pathways in healthy and arthritic SFs. We used a combination of transcriptomic and glycomic analysis to show that transformation of fibroblasts into pro-inflammatory cells in RA is associated with profound glycan remodeling, a process that involves reduction of α2-6 terminal sialylation that is mostly mediated by TNFα-dependent inhibition of the glycosyltransferase ST6Gal1. We also show that sialylation of SFs correlates with distinct disease stages and SFs functional subsets in both human RA and models of mouse arthritis. We propose that pro-inflammatory cytokines in the joint remodel the SF-glycome, transforming a regulatory tissue intended to preserve local homeostasis, into an under-sialylated and highly pro-inflammatory microenvironment that contributes to an amplificatory inflammatory network that perpetuates chronic inflammation. These results highlight the importance of cell glycosylation in stromal immunology.

Investigation of an injectable gold nanoparticle extracellular matrix

2021 ◽  
pp. 088532822110515
Author(s):  
Colten Snider ◽  
David Grant ◽  
Sheila A Grant
Keyword(s):  
Extracellular Matrix ◽  
Synovial Fibroblasts ◽  
X Ray ◽  
Decellularized Extracellular Matrix ◽  
Intracellular Ros ◽  
Murine Fibroblasts ◽  
Post Traumatic ◽  
Injection Force ◽  
20 Nm

Post-traumatic osteoarthritis (PTOA) is a progressive articular degenerative disease that degrades articular cartilage and stimulates apoptosis in chondrocyte cells. An injectable decellularized, extracellular matrix (ECM) scaffold, that might be able to combat the effects of PTOA, was developed where the ECM was conjugated with 20 nm gold nanoparticles (AuNP) and supplemented with curcumin and hyaluronic acid (HA). Porcine diaphragm ECM was decellularized and homogenized; AuNPs were conjugated using chemical crosslinking followed by mixing with curcumin and/or HA. Injection force testing and scanning electron microscopy with energy-dispersive X-ray spectroscopy were utilized to characterize the ECM scaffolds. In vitro testing with L929 murine fibroblasts, equine synovial fibroblasts, and Human Chondrocytes were used to determine biocompatibility, reactive oxygen species (ROS) reduction, and chondroprotective ability. The results demonstrated that conjugation of 20 nm AuNPs to the ECM was successful without significantly altering the physical properties as noted in the low injection force. In vitro work provided evidence of biocompatibility with a propensity to reduce intracellular ROS and an ability to mitigate apoptosis of chondrocyte cells stimulated with IL-1β, a known apoptosis inducing cytokine. It was concluded that an injectable AuNP-ECM may have the ability to mitigate inflammation and apoptosis.

scholarly journals Non-terminal animal model of post-traumatic osteoarthritis induced by acute joint injury

2013 ◽  
Vol 21 (5) ◽  
pp. 746-755 ◽  
Author(s):  
M.K. Boyce ◽  
T.N. Trumble ◽  
C.S. Carlson ◽  
D.M. Groschen ◽  
K.A. Merritt ◽  
...  
Keyword(s):  
Animal Model ◽  
Joint Injury ◽  
Post Traumatic

scholarly journals A Method and Mechanism for Harvesting Intact Autograft for Osteochondral Transplantation

2019 ◽  
Author(s):  
Pradipta Biswas ◽  
Sakura Sikander ◽  
Pankaj Kulkarni ◽  
Sang-Eun Song
Keyword(s):  
Bone Graft ◽  
Donor Site ◽  
Autologous Transplantation ◽  
Removal Mechanism ◽  
Osteochondral Transplantation ◽  
Joint Injury ◽  
Wear And Tear ◽  
Donor Graft ◽  
Graft Removal ◽  
Post Traumatic

Cartilage plays an important role in reducing mechanical stress and assist with smooth limb movement. Osteoarthritis is the degeneration of articular cartilage and bone. This osteochondral region is difficult to heal because of its dissimilar healing capability, so osteochondral transplantation is the most common method to resolve this issue. Post-traumatic osteoarthritis develops after a joint injury and can damage the cartilage and accelerate its wear and tear. Mosaicplasty is the most widely used method involving transplantation of small cylindrical bone cartilage plugs to fill up the affected region. The success of harvesting a larger and complex shaped graft to replace the damaged osteochondral area lies in effective extraction of the cartilage-bone graft from the donor site. Currently, no method exists to perform this procedure for autologous transplantation due to the complexity involved to extract graft without damaging the donor site. In this paper, we propose a novel graft removal mechanism to harvest a personalized autologous graft of virtually any shape and size. Our method involves drilling a profile similar to the effected region on the donor site and slicing off the desired cartilage-bone graft from its root to harvest it. We developed a new graft removal mechanism capable of inserting a flexible saw parallel to the transverse plane and slice the graft parallel to the coronal plane to extract a donor graft for autografting procedures.

Sign in / Sign up

Export Citation Format

Share Document