Molecular-Morphological Relationships of the Scaffold Protein FKBP51 and Inflammatory Processes in Knee Osteoarthritis

Knee osteoarthritis (OA) is one of the most prevalent chronic conditions affecting the adult population. OA is no longer thought to come from a purely biomechanical origin but rather one that has been increasingly recognized to include a persistent low-grade inflammatory component. Intra-articular corticosteroid injections (IACSI) have become a widely used method for treating pain in patients with OA as an effective symptomatic treatment. However, as the disease progresses, IACSI become ineffective. FKBP51 is a regulatory protein of the glucocorticoid receptor function and have been shown to be dysregulated in several pathological scenario’s including chronic inflammation. Despite of these facts, to our knowledge, there are no previous studies of the expression and possible role of FKBP51 in OA. We investigated by double and triple immunofluorescence confocal microscopy the cellular and subcellular expression of FKBP51 and its relations with inflammation factors in osteoarthritic knee joint tissues: specifically, in the tibial plateau knee cartilage, Hoffa’s fat pad and suprapatellar synovial tissue of the knee. Our results show co-expression of FKBP51 with TNF-α, IL-6, CD31 and CD34 in OA chondrocytes, synovial membrane cells and adipocytes in Hoffa’s fat pad. FKBP51 is also abundant in nerve fibers within the fat pad. Co-expression of FKBP51 protein with these markers may be indicative of its contribution to inflammatory processes and associated chronic pain in OA.

Download Full-text

Quantitative DCE-MRI Demonstrates Increased Blood Perfusion in Hoffa’s Fat Pad Signal Abnormalities in Knee Osteoarthritis

10.1055/s-0040-1722501 ◽

2020 ◽

Author(s):

B. A. de Vries ◽

R. V.D. van der Heijden ◽

D. Poot ◽

M. van Middelkoop ◽

D. Meufels ◽

...

Keyword(s):

Knee Osteoarthritis ◽

Blood Perfusion ◽

Fat Pad ◽

Dce Mri ◽

Hoffa’S Fat Pad

Download Full-text

Quantitative DCE-MRI demonstrates increased blood perfusion in Hoffa’s fat pad signal abnormalities in knee osteoarthritis, but not in patellofemoral pain

European Radiology ◽

10.1007/s00330-020-06671-6 ◽

2020 ◽

Vol 30 (6) ◽

pp. 3401-3408 ◽

Cited By ~ 1

Author(s):

Bas A. de Vries ◽

Rianne A. van der Heijden ◽

Dirk H. J. Poot ◽

Marienke van Middelkoop ◽

Duncan E. Meuffels ◽

...

Keyword(s):

Knee Osteoarthritis ◽

Blood Perfusion ◽

Patellofemoral Pain ◽

Fat Pad ◽

Dce Mri ◽

Hoffa’S Fat Pad

Download Full-text

Hoffa’s Fat Pad Abnormality in the Development of Knee Osteoarthritis

Advances in Experimental Medicine and Biology - Current Concepts in Medical Research and Practice ◽

10.1007/5584_2017_77 ◽

2017 ◽

pp. 95-102 ◽

Cited By ~ 1

Author(s):

Wojciech Paduszyński ◽

Mateusz Jeśkiewicz ◽

Paweł Uchański ◽

Sebastian Gackowski ◽

Marek Radkowski ◽

...

Keyword(s):

Knee Osteoarthritis ◽

Fat Pad ◽

Hoffa’S Fat Pad

Download Full-text

Quantitative DCE-MRI demonstrates increased blood perfusion in Hoffa’s fat pad signal abnormalities in knee osteoarthritis, but not in patellofemoral pain

10.26226/morressier.5ee7788d8ba89b7c87c300c6 ◽

2020 ◽

Author(s):

Rianne van der Heijden

Keyword(s):

Knee Osteoarthritis ◽

Blood Perfusion ◽

Patellofemoral Pain ◽

Fat Pad ◽

Dce Mri ◽

Hoffa’S Fat Pad

Download Full-text

Inflammageing in the cardiovascular system: mechanisms, emerging targets, and novel therapeutic strategies

Clinical Science ◽

10.1042/cs20191213 ◽

2020 ◽

Vol 134 (17) ◽

pp. 2243-2262

Author(s):

Danlin Liu ◽

Gavin Richardson ◽

Fehmi M. Benli ◽

Catherine Park ◽

João V. de Souza ◽

...

Keyword(s):

Cardiovascular Diseases ◽

Cardiovascular System ◽

Nlrp3 Inflammasome ◽

Molecular Mechanisms ◽

Molecular Targets ◽

Therapeutic Interventions ◽

Low Grade ◽

Cardiovascular Research ◽

Inflammatory Processes ◽

Ach Receptors

Abstract In the elderly population, pathological inflammation has been associated with ageing-associated diseases. The term ‘inflammageing’, which was used for the first time by Franceschi and co-workers in 2000, is associated with the chronic, low-grade, subclinical inflammatory processes coupled to biological ageing. The source of these inflammatory processes is debated. The senescence-associated secretory phenotype (SASP) has been proposed as the main origin of inflammageing. The SASP is characterised by the release of inflammatory cytokines, elevated activation of the NLRP3 inflammasome, altered regulation of acetylcholine (ACh) nicotinic receptors, and abnormal NAD+ metabolism. Therefore, SASP may be ‘druggable’ by small molecule therapeutics targeting those emerging molecular targets. It has been shown that inflammageing is a hallmark of various cardiovascular diseases, including atherosclerosis, hypertension, and adverse cardiac remodelling. Therefore, the pathomechanism involving SASP activation via the NLRP3 inflammasome; modulation of NLRP3 via α7 nicotinic ACh receptors; and modulation by senolytics targeting other proteins have gained a lot of interest within cardiovascular research and drug development communities. In this review, which offers a unique view from both clinical and preclinical target-based drug discovery perspectives, we have focused on cardiovascular inflammageing and its molecular mechanisms. We have outlined the mechanistic links between inflammageing, SASP, interleukin (IL)-1β, NLRP3 inflammasome, nicotinic ACh receptors, and molecular targets of senolytic drugs in the context of cardiovascular diseases. We have addressed the ‘druggability’ of NLRP3 and nicotinic α7 receptors by small molecules, as these proteins represent novel and exciting targets for therapeutic interventions targeting inflammageing in the cardiovascular system and beyond.

Download Full-text

Obstructive Sleep Apnea and Inflammation: Proof of Concept Based on Two Illustrative Cytokines

International Journal of Molecular Sciences ◽

10.3390/ijms20030459 ◽

2019 ◽

Vol 20 (3) ◽

pp. 459 ◽

Cited By ~ 31

Author(s):

Leila Kheirandish-Gozal ◽

David Gozal

Keyword(s):

Obstructive Sleep Apnea ◽

Sleep Apnea ◽

Inflammatory Diseases ◽

Sleep Apnea Syndrome ◽

Special Focus ◽

Normal Body Mass Index ◽

Low Grade ◽

Obstructive Sleep ◽

Inflammatory Processes ◽

Factor Α

Obstructive sleep apnea syndrome (OSAS) is a markedly prevalent condition across the lifespan, particularly in overweight and obese individuals, which has been associated with an independent risk for neurocognitive, behavioral, and mood problems as well as cardiovascular and metabolic morbidities, ultimately fostering increases in overall mortality rates. In adult patients, excessive daytime sleepiness (EDS) is the most frequent symptom leading to clinical referral for evaluation and treatment, but classic EDS features are less likely to be reported in children, particularly among those with normal body-mass index. The cumulative evidence collected over the last two decades supports a conceptual framework, whereby sleep-disordered breathing in general and more particularly OSAS should be viewed as low-grade chronic inflammatory diseases. Accordingly, it is assumed that a proportion of the morbid phenotypic signature in OSAS is causally explained by underlying inflammatory processes inducing end-organ dysfunction. Here, the published links between OSAS and systemic inflammation will be critically reviewed, with special focus on the pro-inflammatory cytokines tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6), since these constitute classical prototypes of the large spectrum of inflammatory molecules that have been explored in OSAS patients.

Download Full-text

AB0862 CONSENSUS STATEMENT ON INTRA-ARTICULAR INJECTIONS OF PLATELET-RICH PLASMA FOR THE MANAGEMENT OF KNEE OSTEOARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.618 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1738.3-1738

Author(s):

F. Eymard ◽

P. Ornetti ◽

J. Maillet ◽

E. Noel ◽

P. Adam ◽

...

Keyword(s):

Knee Osteoarthritis ◽

Task Force ◽

Platelet Rich Plasma ◽

Symptomatic Treatment ◽

Future Research ◽

List Type ◽

Clinical Practices ◽

Efficient Treatment ◽

Symptomatic Knee Osteoarthritis ◽

Symptomatic Knee

Background:There has been much debate regarding the use of intra-articular injections of platelet-rich plasma (PRP) as symptomatic treatment for knee osteoarthritis. The heterogeneity of the preparation and injection protocols limits the extrapolation of data from randomized controlled trials and meta-analyses.Objectives:The objective of this expert consensus was to develop the first clinical practice recommendations for PRP injections in knee osteoarthritis.Methods:Fifteen physicians (10 rheumatologists, 4 specialists in rehabilitation and sport medicine and 1 interventional radiologist) from different countries were selected given to their expertise in the fields of PRP and osteoarthritis. Twenty-five recommendations were finally retained after several meetings using the modified Delphi method to establish clinical consensus. All experts voted their agreement or not for each recommendation using a score between 1 (totally inappropriate) and 9 (totally appropriate). Depending on the median value and extreme scores, recommendations were judged as appropriated or unappropriated with a strong or relative agreement but could also be judged as uncertain due to indecision or absence of consensus.Results:The main recommendations are listed below:- Intra-articular injections of PRP constitute an efficient treatment of early or moderate symptomatic knee osteoarthritis. Median = 8 [6-9] – Appropriate. Relative agreement.- Intra-articular injections of PRP may be useful in severe knee osteoarthritis (Kellgren-Lawrence grade IV). Median = 7 [6-7] – Appropriate. Relative agreement.- Intra-articular injections of PRP in knee osteoarthritis should be proposed as second-line therapy, after failure of non-pharmacological and pharmacological (oral and topic) symptomatic treatment. Median = 9 [5-9] – Appropriate. Relative agreement.- Intra-articular injections of PRP should not be performed in osteoarthritis flare-up with significant effusion. Median = 7 [5-9] – Appropriate. Relative agreement.- Intra-articular PRP treatment may include 1 to 3 consecutive injections. Median = 9 [7-9] – Appropriate. Strong agreement.- Leukocyte-poor PRP should be preferred for knee OA treatment. Median = 8 [5-9] – Appropriate. Relative agreement.- PRP injections should be performed under ultrasound or fluoroscopic guidance. Median = 8 [3-9] – Uncertain. No consensus.- PRP should not be mixed with injectable anesthetic or corticosteroid. Median = 9 [6-9] – Appropriate. Relative agreement.Conclusion:Twenty-five recommendations were discussed by an international multidisciplinary task force group in order to provide a basis for standardization of clinical practices and future research protocols.Disclosure of Interests:Florent Eymard Consultant of: Regenlab, Paul Ornetti: None declared, Jérémy Maillet Consultant of: Regenlab, Eric Noel Consultant of: Regenlab, Philippe Adam Consultant of: Regenlab, Virginie Legré Boyer Consultant of: Regenlab, Thierry Boyer Consultant of: Regenlab, Fadoua Allali: None declared, Vincent Grémeaux Bader: None declared, Jean-François Kaux: None declared, Karine Louati: None declared, Martin Lamontagne Consultant of: Pendopharm, Fabrice Michel: None declared, Pascal Richette: None declared, Hervé Bard Consultant of: Regenlab

Download Full-text