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Keywords = calcium pyrophosphate crystals

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9 pages, 441 KiB  
Article
Persistence of Monosodium Urate Crystals and Calcium Pyrophosphate Crystals in Synovial Fluid Samples After Two Weeks of Storage at 4 °C and −20 °C: A Longitudinal Analysis
by Kanon Jatuworapruk, Jassdakorn Suaypring, Natrawee Ngamprasertsith and Nattawat Watcharajittanont
Gout Urate Cryst. Depos. Dis. 2025, 3(3), 12; https://doi.org/10.3390/gucdd3030012 - 3 Jul 2025
Viewed by 321
Abstract
Objectives: Identification of monosodium urate (MSU) and calcium pyrophosphate (CPP) crystals in synovial fluid should ideally be performed within 24 h to ensure optimal diagnostic accuracy for gout and CPP arthritis. However, crystal identification is often delayed in community-based healthcare facilities due to [...] Read more.
Objectives: Identification of monosodium urate (MSU) and calcium pyrophosphate (CPP) crystals in synovial fluid should ideally be performed within 24 h to ensure optimal diagnostic accuracy for gout and CPP arthritis. However, crystal identification is often delayed in community-based healthcare facilities due to limited access to specialists or necessary equipment. This study aimed to determine whether MSU and CPP crystals remain detectable in synovial fluid after two weeks of storage at 4 °C and −20 °C. Methods: Anonymized synovial fluid samples were obtained from Thammasat University Hospital between February and March 2024. All samples underwent an initial round of crystal identification using compensated polarized light microscopy, conducted by two experienced examiners blinded to the clinical diagnosis. Following the initial analysis, each sample was divided into two equal portions and placed in ethylenediaminetetraacetic acid (EDTA)-coated tubes. One portion was stored at 4 °C, while the other was frozen at −20 °C. After two weeks, all samples underwent a second round of crystal identification. Results: Forty-nine samples were included for the first evaluation; MSU and CPP crystals were identified in 14 and 6 samples, respectively. On the second examination, MSU crystals were detectable in 13/14 (92.8%) samples stored at 4 °C and 12/14 (85.7%) samples stored at −20 °C. However, CPP crystals were detectable in 2/6 (33.3%) samples stored at both temperatures. No new crystal formation in initially negative samples was observed. Conclusion: MSU crystals remain detectable in synovial fluid for up to two weeks when stored in a standard refrigerator or freezer. However, the identification rate of CPP crystals tends to decline over this period. These findings may help inform best practices for handling synovial fluid samples in cases where immediate access to a specialist or necessary equipment is unavailable. Full article
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15 pages, 4918 KiB  
Review
Ultrasonographic Assessment of Calcium Pyrophosphate Deposition Disease: A Comprehensive Review
by Lissiane Karine Noronha Guedes, Letícia Queiroga de Figueiredo, Fernanda Oliveira de Andrade Lopes, Luis Fernando Fernandes Ferrari and Karina Rossi Bonfiglioli
J. Pers. Med. 2025, 15(7), 280; https://doi.org/10.3390/jpm15070280 - 1 Jul 2025
Viewed by 299
Abstract
Calcium pyrophosphate deposition disease (CPPD) is a common crystal arthropathy characterized by the deposition of calcium pyrophosphate crystals in joints and soft tissues. Ultrasonography (US) has emerged as a valuable imaging modality for diagnosing CPPD, offering real-time visualization of crystal deposits and joint [...] Read more.
Calcium pyrophosphate deposition disease (CPPD) is a common crystal arthropathy characterized by the deposition of calcium pyrophosphate crystals in joints and soft tissues. Ultrasonography (US) has emerged as a valuable imaging modality for diagnosing CPPD, offering real-time visualization of crystal deposits and joint inflammation. In the context of personalized medicine, US plays a critical role in enabling individualized patient assessment, facilitating early and accurate diagnosis, and supporting tailored therapeutic decisions based on specific imaging findings. This article reviews the ultrasonographic features of CPPD, their diagnostic utility, and clinical applications, emphasizing the relevance of US in stratifying patients and guiding personalized management approaches. Full article
(This article belongs to the Special Issue Personalized Medicine for Rheumatic Diseases)
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22 pages, 2757 KiB  
Review
Comparison of Pathophysiological Mechanisms Among Crystal-Induced Arthropathies
by Maddalena Zangari, Roberto Luisetto, Roberto Pilot, Paola Contessa, Raffaella Signorini, Stefano Masiero and Anna Scanu
Gout Urate Cryst. Depos. Dis. 2025, 3(2), 7; https://doi.org/10.3390/gucdd3020007 - 10 Apr 2025
Viewed by 1794
Abstract
Monosodium urate, calcium pyrophosphate, and basic calcium phosphate crystals are the most common types of crystals found in the joints. Each type of crystal has been associated with the onset of different joint diseases. However, the mechanisms identified for one type of crystal [...] Read more.
Monosodium urate, calcium pyrophosphate, and basic calcium phosphate crystals are the most common types of crystals found in the joints. Each type of crystal has been associated with the onset of different joint diseases. However, the mechanisms identified for one type of crystal are often generalized to the others; thus, overlooking the specific and distinct molecular and cellular responses activated by each type of crystal. This review describes the similarities and differences of the main molecules and mechanisms underlying the diseases associated with the three different types of crystals. Specifically, current knowledge on crystal properties and formation, on the induction and resolution of inflammation, on mechanisms involved in pain processing and senescence, and on the role of mitochondria and genomic instability are elucidated. A more complete and detailed study of the specific molecular mechanisms induced by different crystals is necessary to advance our understanding of the pathogenesis and to help identify innovative opportunities for prevention and treatment of crystal deposition disease. Full article
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12 pages, 714 KiB  
Article
Predominance of Calcium Pyrophosphate Crystals in Synovial Fluid Samples of Patients at a Large Tertiary Center
by Tobias Manigold and Alexander Leichtle
Diagnostics 2025, 15(7), 907; https://doi.org/10.3390/diagnostics15070907 - 1 Apr 2025
Viewed by 2625
Abstract
Background: Crystal arthritides represent the most common inflammatory rheumatologic condition. While the prevalence of gouty arthritis by monosodium urate (MSU) is well established, the prevalences of calciumpyrophosphat (CPP) and basic calcium pyrophosphate (ARP) arthritis are less clear. We herein sought to assess the [...] Read more.
Background: Crystal arthritides represent the most common inflammatory rheumatologic condition. While the prevalence of gouty arthritis by monosodium urate (MSU) is well established, the prevalences of calciumpyrophosphat (CPP) and basic calcium pyrophosphate (ARP) arthritis are less clear. We herein sought to assess the prevalence and inflammatory characteristics of crystal arthritides at our institution, the biggest tertiary center in Switzerland. Methods: A total of 5036 synovial fluid (SF) samples were analyzed with regard to crystal positivity as well as joint, age, and sex distribution in affected patients. We furthermore compared inflammatory and non-inflammatory SF samples for yields of their Polymorphonuclear (PMN) fractions. Results: About half of all samples were derived from knee joints, a male/female ratio up to 10.1:1 among the MSU-positive, and a clear shift towards elder patients with CPP–arthritis was seen. These findings were in line with previous studies and suggest good comparability of our cohort. Of note, 21.9% of all samples were CPP positive, whereas 15.3% and 9.5% were positive for MSU and ARP/alizarin-red positive, respectively. Importantly, CPP crystals were predominant in inflammatory (58.9%) and non-inflammatory (65.7%) samples. By contrast, MSU crystals were significantly more often associated with synovitis (p < 0.001). Interestingly, higher PMN fractions were found in non-inflammatory MSU-positive samples (p < 0.01), whereas a similar trend was seen in CPP-positive samples. Conclusions: CPP arthritis represented the most frequent crystal arthritis form at our center. Higher PMN fractions in non-inflammatory samples with CPP and MSU crystals suggest subclinical inflammation and provide further arguments for earlier anti-inflammatory and uric acid-lowering therapies in patients with crystal deposits. Full article
(This article belongs to the Section Clinical Laboratory Medicine)
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6 pages, 291 KiB  
Article
Higher Rates of Psoriatic Arthritis in Patients with Calcium Pyrophosphate Deposition Disease than in Controls: A Retrospective Cohort Study
by Natalie Anumolu, Ann Rosenthal, Katherine Sherman and Shikha Singla
Gout Urate Cryst. Depos. Dis. 2025, 3(2), 5; https://doi.org/10.3390/gucdd3020005 - 27 Mar 2025
Viewed by 603
Abstract
Calcium pyrophosphate deposition disease (CPPD) has been shown to be associated with inflammatory arthritis such as rheumatoid arthritis. However, few studies have investigated the correlation between CPPD and psoriatic arthritis (PsA). Our study aimed to determine whether there were higher rates of PsA [...] Read more.
Calcium pyrophosphate deposition disease (CPPD) has been shown to be associated with inflammatory arthritis such as rheumatoid arthritis. However, few studies have investigated the correlation between CPPD and psoriatic arthritis (PsA). Our study aimed to determine whether there were higher rates of PsA in patients with CPPD than controls. A retrospective cohort study was conducted using the Veterans Affairs’ Corporate Data Warehouse. Individuals with a CPPD ICD code were matched with controls and diagnoses of PsA and psoriasis were collected. A total of 41,084 CPPD patients were matched with 119,192 controls. The proportion of CPPD patients with PsA diagnosis was more than double that of controls (1.07% vs. 0.37%; p < 0.0001), and more CPPD patients were diagnosed with psoriasis (3.05% vs. 2.52%; p < 0.0001). Those with CPPD had higher odds of a PsA diagnosis (OR 3.550, 95% CI 2.602–4.844). A total of 61.59% of PsA diagnoses preceded the CPPD diagnoses by at least one year. This is the first case–control study demonstrating an association between CPPD and PsA, potentially related to the fact that both PsA and CPPD could be triggered by trauma, and are closely associated with osteoarthritis. It also is possible that inflammatory pathways contribute to CPP crystal deposition in joints. Full article
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10 pages, 2065 KiB  
Review
Physiopathological Aspects of Synovial Fluid and Membrane in Psoriatic Arthritis
by Amelia Carmela Damasco, Roberta Ramonda, Giacomo Cozzi, Mariagrazia Lorenzin, Paolo Sfriso, Francesca Oliviero and Chiara Baggio
Rheumato 2024, 4(4), 193-202; https://doi.org/10.3390/rheumato4040015 - 5 Nov 2024
Viewed by 1670
Abstract
Background: Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy characterized by a variety of clinical manifestations, mainly affecting joints and entheses, but also skin, nails, the eye, and the intestine. Objectives: In this review, we describe the essential characteristics of both synovial membranes [...] Read more.
Background: Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy characterized by a variety of clinical manifestations, mainly affecting joints and entheses, but also skin, nails, the eye, and the intestine. Objectives: In this review, we describe the essential characteristics of both synovial membranes and synovial fluid (SF) in PsA. Similarly to other inflammatory arthritis, the histological peculiarities in PsA synovitis are lining hyperplasia, neoangiogenesis, and sublining infiltration by immune cells and inflammatory mediators. Synovial effusions are frequent in PsA patients and SF analysis allows us to determine the pathological process occurring in the joint. Routine examinations help clinicians in defining the inflammatory status and possibly the detection of specific cell subsets. In addition, pathogenic crystals including monosodium urate and calcium pyrophosphate may be found in PsA SF. Conclusions: SF represents a potential substrate to identify the biomarkers that are useful to predict disease progression and response to medications in PsA patients, thus guiding the choice of appropriate and tailored pharmacological treatment. Full article
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10 pages, 1713 KiB  
Article
A Novel Polarized Light Microscope for the Examination of Birefringent Crystals in Synovial Fluid
by John D. FitzGerald, Chesca Barrios, Tairan Liu, Ann Rosenthal, Geraldine M. McCarthy, Lillian Chen, Bijie Bai, Guangdong Ma and Aydogan Ozcan
Gout Urate Cryst. Depos. Dis. 2024, 2(4), 315-324; https://doi.org/10.3390/gucdd2040022 - 22 Oct 2024
Cited by 1 | Viewed by 3465
Abstract
Background: The gold standard for crystal arthritis diagnosis relies on the identification of either monosodium urate (MSU) or calcium pyrophosphate (CPP) crystals in synovial fluid. With the goal of enhanced crystal detection, we adapted a standard compensated polarized light microscope (CPLM) with a [...] Read more.
Background: The gold standard for crystal arthritis diagnosis relies on the identification of either monosodium urate (MSU) or calcium pyrophosphate (CPP) crystals in synovial fluid. With the goal of enhanced crystal detection, we adapted a standard compensated polarized light microscope (CPLM) with a polarized digital camera and multi-focal depth imaging capabilities to create digital images from synovial fluid mounted on microscope slides. Using this single-shot computational polarized light microscopy (SCPLM) method, we compared rates of crystal detection and raters’ preference for image. Methods: Microscope slides from patients with either CPP, MSU, or no crystals in synovial fluid were acquired using CPLM and SCPLM methodologies. Detection rate, sensitivity, and specificity were evaluated by presenting expert crystal raters with (randomly sorted) CPLM and SCPLM digital images, from FOV above clinical samples. For each FOV and each method, each rater was asked to identify crystal suspects and their level of certainty for each crystal suspect and crystal type (MSU vs. CPP). Results: For the 283 crystal suspects evaluated, SCPLM resulted in higher crystal detection rates than did CPLM, for both CPP (51%. vs. 28%) and MSU (78% vs. 46%) crystals. Similarly, sensitivity was greater for SCPLM for CPP (0.63 vs. 0.35) and MSU (0.88 vs. 0.52) without giving up much specificity resulting in higher AUC. Conclusions: Subjective and objective measures of greater detection and higher certainty were observed for SCPLM over CPLM, particularly for CPP crystals. The digital data associated with these images can ultimately be incorporated into an automated crystal detection system that provides a quantitative report on crystal count, size, and morphology. Full article
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26 pages, 2883 KiB  
Review
Practical Use of Ultrasound in Modern Rheumatology—From A to Z
by Tanya Sapundzhieva, Lyubomir Sapundzhiev and Anastas Batalov
Life 2024, 14(9), 1208; https://doi.org/10.3390/life14091208 - 23 Sep 2024
Cited by 3 | Viewed by 2973
Abstract
During the past 20 years, the use of ultrasound (US) in rheumatology has increased tremendously, and has become a valuable tool in rheumatologists’ hands, not only for assessment of musculoskeletal structures like joints and peri-articular tissues, but also for evaluation of nerves, vessels, [...] Read more.
During the past 20 years, the use of ultrasound (US) in rheumatology has increased tremendously, and has become a valuable tool in rheumatologists’ hands, not only for assessment of musculoskeletal structures like joints and peri-articular tissues, but also for evaluation of nerves, vessels, lungs, and skin, as well as for increasing the accuracy in a number of US-guided aspirations and injections. The US is currently used as the imaging method of choice for establishing an early diagnosis, assessing disease activity, monitoring treatment efficacy, and assessing the remission state of inflammatory joint diseases. It is also used as a complementary tool for the assessment of patients with degenerative joint diseases like osteoarthritis, and in the detection of crystal deposits for establishing the diagnosis of metabolic arthropathies (gout, calcium pyrophosphate deposition disease). The US has an added value in the diagnostic process of polymyalgia rheumatica and giant-cell arteritis, and is currently included in the classification criteria. A novel use of US in the assessment of the skin and lung involvement in connective tissue diseases has the potential to replace more expensive and risky imaging modalities. This narrative review will take a close look at the most recent evidence-based data regarding the use of US in the big spectrum of rheumatic diseases. Full article
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16 pages, 732 KiB  
Review
Age-Associated Calcification: Insights from Murine Models
by Sonia Nasi, Mario Romani and Nathalie Busso
Gout Urate Cryst. Depos. Dis. 2024, 2(3), 236-251; https://doi.org/10.3390/gucdd2030018 - 6 Aug 2024
Cited by 2 | Viewed by 3583
Abstract
Calcification refers to the deposition of calcium-containing crystals either intracellularly or within the extracellular matrix. Physiologic calcification is a normal process occurring during bone and tooth development and growth. In contrast, pathologic calcification occurs in soft tissues that typically do not undergo mineralization, [...] Read more.
Calcification refers to the deposition of calcium-containing crystals either intracellularly or within the extracellular matrix. Physiologic calcification is a normal process occurring during bone and tooth development and growth. In contrast, pathologic calcification occurs in soft tissues that typically do not undergo mineralization, such as blood vessels, cartilage, tendons, and skin. Pathological calcification is significantly associated with tissue impairment and the development of secondary diseases, such as atherosclerosis, osteoarthritis, tendinopathy, and skin ulcers. Aging, a natural process linked to numerous pathologic conditions, is one of the most recognized risk factors for pathological calcification. In this manuscript, we review the current state of knowledge regarding the role of aging in calcification across different tissues. We focus on the mechanisms activated during normal aging, including cellular senescence, decreased pyrophosphate levels, increased secretion of extracellular vesicles, elevated oxidative stress, and higher levels of pro-mineralizing cytokines, all of which can contribute to pathological calcification. Finally, we discuss the available animal models used to study the impact of aging on calcification. Full article
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16 pages, 2480 KiB  
Article
Synovial Membrane Is a Major Producer of Extracellular Inorganic Pyrophosphate in Response to Hypoxia
by Émilie Velot, Sylvie Sébillaud and Arnaud Bianchi
Pharmaceuticals 2024, 17(6), 738; https://doi.org/10.3390/ph17060738 - 5 Jun 2024
Cited by 1 | Viewed by 1223
Abstract
Calcium pyrophosphate dehydrate (CPPD) crystals are found in the synovial fluid of patients with articular chondrocalcinosis or sometimes with osteoarthritis. In inflammatory conditions, the synovial membrane (SM) is subjected to transient hypoxia, especially during movement. CPPD formation is supported by an increase in [...] Read more.
Calcium pyrophosphate dehydrate (CPPD) crystals are found in the synovial fluid of patients with articular chondrocalcinosis or sometimes with osteoarthritis. In inflammatory conditions, the synovial membrane (SM) is subjected to transient hypoxia, especially during movement. CPPD formation is supported by an increase in extracellular inorganic pyrophosphate (ePPi) levels, which are mainly controlled by the transporter Ank and ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1). We demonstrated previously that transforming growth factor (TGF)-β1 increased ePPi production by inducing Ank and Enpp1 expression in chondrocytes. As the TGF-β1 level raises in synovial fluid under hypoxic conditions, we investigated whether hypoxia may transform SM as a major source of ePPi production. Synovial fibroblasts and SM explants were exposed to 10 ng/mL of TGF-β1 in normoxic or hypoxic (5% O2) culture conditions. Ank and Enpp1 expression were assessed by quantitative PCR, Western blot and immunohistochemistry. ePPi was quantified in culture supernatants. RNA silencing was used to define the respective roles of Ank and Enpp1 in TGF-β1-induced ePPi generation. The molecular mechanisms involved in hypoxia were investigated using an Ank promoter reporter plasmid for transactivation studies, as well as gene overexpression and RNA silencing, the respective role of hypoxia-induced factor (HIF)-1 and HIF-2. Our results showed that TGF-β1 increased Ank, Enpp1, and therefore ePPi production in synovial fibroblasts and SM explants. Ank was the major contributor in ePPi production compared to ENPP1. Hypoxia increased ePPi levels on its own and enhanced the stimulating effect of TGF-β1. Hypoxic conditions enhanced Ank promoter transactivation in an HIF-1-dependent/HIF-2-independent fashion. We demonstrated that under hypoxia, SM is an important contributor to ePPi production in the joint through the induction of Enpp1 and Ank. These findings are of interest as a rationale for the beneficial effect of anti-inflammatory drugs on SM in crystal depositions. Full article
(This article belongs to the Section Pharmacology)
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7 pages, 230 KiB  
Review
Calcium Pyrophosphate and Basic Calcium Phosphate Crystal Arthritis: 2023 in Review
by Augustin Latourte, Hang-Korng Ea and Pascal Richette
Gout Urate Cryst. Depos. Dis. 2024, 2(2), 101-107; https://doi.org/10.3390/gucdd2020010 - 5 Apr 2024
Cited by 10 | Viewed by 2389
Abstract
Calcium-containing crystal deposition diseases are extremely common in rheumatology. However, they are under-explored compared to gout or other inflammatory rheumatic diseases. Major advances have been made in 2023 that will undoubtedly stimulate and facilitate research in the field of calcium pyrophosphate (CPP) deposition [...] Read more.
Calcium-containing crystal deposition diseases are extremely common in rheumatology. However, they are under-explored compared to gout or other inflammatory rheumatic diseases. Major advances have been made in 2023 that will undoubtedly stimulate and facilitate research in the field of calcium pyrophosphate (CPP) deposition disease (CPPD): the ACR/EULAR classification criteria for CPPD and a semi-quantitative OMERACT score for ultrasound assessment of the extent of CPP deposition have been validated and published. A large randomized controlled trial compared the efficacy and safety of colchicine and prednisone in acute CPP arthritis. Preclinical studies have elucidated the pro-inflammatory and anti-catabolic effects of basic calcium phosphate (BCP) crystals on mononuclear cells and chondrocytes. The association between osteoarthritis (OA) and IA calcifications has been the subject of several epidemiological publications, suggesting that calcium crystals are associated with a greater risk of progression of knee OA. Research in the field of calcium crystal deposition diseases is active: the areas of investigation for the coming years are broad and promising. Full article
17 pages, 7783 KiB  
Article
Osteostatin Mitigates Gouty Arthritis through the Inhibition of Caspase-1 Activation and Upregulation of Nrf2 Expression
by Laura Catalán, María Carmen Carceller, María Carmen Terencio, María José Alcaraz, María Luisa Ferrándiz and María Carmen Montesinos
Int. J. Mol. Sci. 2024, 25(5), 2752; https://doi.org/10.3390/ijms25052752 - 27 Feb 2024
Cited by 6 | Viewed by 2350
Abstract
Gouty arthritis results from monosodium urate (MSU) crystal deposition in joints, initiating (pro)-interleukin (IL)-1β maturation, inflammatory mediator release, and neutrophil infiltration, leading to joint swelling and pain. Parathyroid hormone-related protein (107–111) C-terminal peptide (osteostatin) has shown anti-inflammatory properties in osteoblasts and collagen-induced arthritis [...] Read more.
Gouty arthritis results from monosodium urate (MSU) crystal deposition in joints, initiating (pro)-interleukin (IL)-1β maturation, inflammatory mediator release, and neutrophil infiltration, leading to joint swelling and pain. Parathyroid hormone-related protein (107–111) C-terminal peptide (osteostatin) has shown anti-inflammatory properties in osteoblasts and collagen-induced arthritis in mice, but its impact in gouty arthritis models remains unexplored. We investigated the effect of osteostatin on pyroptosis, inflammation, and oxidation in macrophages, as well as its role in the formation of calcium pyrophosphate dihydrate crystals and MSU-induced gouty arthritis in mice models. Osteostatin ameliorated pyroptosis induced by lipopolysaccharide and adenosine 5′-triphosphate (LPS + ATP) in mice peritoneal macrophages by reducing the expression of caspase-1, lactate dehydrogenase release, and IL-1β and IL-18 secretion. Additionally, IL-6 and tumor necrosis factor-α (TNF-α) were also decreased due to the reduced activation of the NF-κB pathway. Furthermore, osteostatin displayed antioxidant properties in LPS + ATP-stimulated macrophages, resulting in reduced production of mitochondrial and extracellular reactive oxygen species and enhanced Nrf2 translocation to the nuclei. In both models of gouty arthritis, osteostatin administration resulted in reduced pro-inflammatory cytokine production, decreased leukocyte migration, and reduced caspase-1 and NF-κB activation. These results highlight the potential of osteostatin as a therapeutic option for gouty arthritis. Full article
(This article belongs to the Special Issue State-of-the-Art Molecular Pharmacology in Spain 2.0)
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15 pages, 2672 KiB  
Review
Vascular Calcification: A Passive Process That Requires Active Inhibition
by Ricardo Villa-Bellosta
Biology 2024, 13(2), 111; https://doi.org/10.3390/biology13020111 - 9 Feb 2024
Cited by 17 | Viewed by 4554
Abstract
The primary cause of worldwide mortality and morbidity stems from complications in the cardiovascular system resulting from accelerated atherosclerosis and arterial stiffening. Frequently, both pathologies are associated with the pathological calcification of cardiovascular structures, present in areas such as cardiac valves or blood [...] Read more.
The primary cause of worldwide mortality and morbidity stems from complications in the cardiovascular system resulting from accelerated atherosclerosis and arterial stiffening. Frequently, both pathologies are associated with the pathological calcification of cardiovascular structures, present in areas such as cardiac valves or blood vessels (vascular calcification). The accumulation of hydroxyapatite, the predominant form of calcium phosphate crystals, is a distinctive feature of vascular calcification. This phenomenon is commonly observed as a result of aging and is also linked to various diseases such as diabetes, chronic kidney disease, and several genetic disorders. A substantial body of evidence indicates that vascular calcification involves two primary processes: a passive process and an active process. The physicochemical process of hydroxyapatite formation and deposition (a passive process) is influenced significantly by hyperphosphatemia. However, the active synthesis of calcification inhibitors, including proteins and low-molecular-weight inhibitors such as pyrophosphate, is crucial. Excessive calcification occurs when there is a loss of function in enzymes and transporters responsible for extracellular pyrophosphate metabolism. Current in vivo treatments to prevent calcification involve addressing hyperphosphatemia with phosphate binders and implementing strategies to enhance the availability of pyrophosphate. Full article
(This article belongs to the Special Issue Recent Advances in Vascular Calcification)
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17 pages, 3275 KiB  
Technical Note
Optimizing the Use of Ultrasound in Calcium Pyrophosphate Deposition (CPPD): A Review from the Ground Up
by Georgios Filippou, Silvia Sirotti, Edoardo Cipolletta and Emilio Filippucci
Gout Urate Cryst. Depos. Dis. 2024, 2(1), 17-33; https://doi.org/10.3390/gucdd2010002 - 24 Jan 2024
Cited by 12 | Viewed by 5415
Abstract
Ultrasound is a pivotal exam in calcium pyrophosphate deposition (CPPD) identification. It has been demonstrated to be feasible, accurate, and reliable for CPPD diagnosis. Even if standardized definitions and a scoring system for CPPD have been established by the OMERACT ultrasound working group, [...] Read more.
Ultrasound is a pivotal exam in calcium pyrophosphate deposition (CPPD) identification. It has been demonstrated to be feasible, accurate, and reliable for CPPD diagnosis. Even if standardized definitions and a scoring system for CPPD have been established by the OMERACT ultrasound working group, ultrasound is still considered one of the most operator-dependent techniques. This is because in ultrasound, both the acquisition and the interpretation phases of the diagnostic process are in the hands of one operator and are performed simultaneously, in contrast to what happens with other imaging exams, where the acquisition process is standardized and independent from the interpretation process. Therefore, the scanning technique and machine setting acquire a central role, almost as important as the interpretation of the images, as erroneous scanning may lead to interpretative mistakes. In this review, we will delve into the appearance of CPPD on ultrasound, based on the latest research findings, passing through its pathogenesis, and focusing on machine settings and ultrasound scanning techniques, providing some tips and tricks to facilitate accurate CPPD recognition in the most frequently affected sites. Full article
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10 pages, 3990 KiB  
Article
Synovial Fluid from Patients with Osteoarthritis Shows Different Inflammatory Features Depending on the Presence of Calcium Pyrophosphate Crystals
by Francesca Oliviero, Chiara Baggio, Marta Favero, Amelia Carmela Damasco, Carlotta Boscaro, Davide Tietto, Mattia Albiero, Andrea Doria and Roberta Ramonda
Int. J. Mol. Sci. 2024, 25(1), 393; https://doi.org/10.3390/ijms25010393 - 27 Dec 2023
Cited by 5 | Viewed by 2356
Abstract
The role of calcium pyrophosphate (CPP) crystals in osteoarthritis (OA) is still a matter of debate. With this study we aimed to investigate the inflammatory features of synovial fluid (SF) collected from patients with OA with CPP crystals compared with those without crystals. [...] Read more.
The role of calcium pyrophosphate (CPP) crystals in osteoarthritis (OA) is still a matter of debate. With this study we aimed to investigate the inflammatory features of synovial fluid (SF) collected from patients with OA with CPP crystals compared with those without crystals. We also explored the effect of OA SF on monocytes response. SFs were collected from adult patients with OA and subdivided according to the presence of crystals. Local cellular and humoral inflammatory mediators were analysed in the SF samples. The expression levels of IL-1β, IL-18, CASP-1, NLRP3, and GAPDH were measured by RT-PCR in the cells obtained by pelleting the SF samples. For the in vitro study, a monocytic cell line was treated with selected SF samples. SF with CPP crystals showed a significant increase in inflammatory cellular indices and higher levels of IL-1β, IL-8, and caspase-1 transcript with respect to SF without crystals. Higher concentrations of VEGF were also observed in the early stages of the whole OA patients. THP-1 cells stimulated with OA SF released a significant amount of IL-1 β in culture supernatants. This study demonstrated that SF collected from patients with OA shows different inflammatory features depending on the presence of CPP crystals. Full article
(This article belongs to the Special Issue Osteoarthritis: From Pathogenesis to Treatment)
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