Gout Urate Cryst. Depos. Dis., Volume 2, Issue 3 (September 2024) – 4 articles

Periarticular calcifications are a common condition for rheumatologists. They are characterized by deposition of carbonated apatite in tendons or connective tissues around joints. It most commonly affects patients between 30 and 60, and the main location is the shoulder (rotator cuff tendons), followed by the hip. Although the disease is frequent, factors associated with the appearance of the deposits or their spontaneous resorption remain unclear. In this review, we will summarize the available data about mechanisms underlying the constitution of the deposits and their resorption and describe the various affected sites and the associated symptoms. In the last part, we will discuss current treatment options. Full article

Many preclinical reports have coalesced to identify a strong association between obesity and increased levels of uric acid (UA) in tissues and, importantly, in the circulation (hyperuricemia). Unfortunately, nearly all these studies were conducted with male mice or, in one case, female mice without a side-by-side male cohort. Therefore, the relationship between obesity and hyperuricemia in female mice remains undefined. This lack of clarity in the field has considerable impact as the downstream effects of obesity and allied hyperuricemia are extensive, resulting in many comorbidities including cardiovascular dysfunction, chronic kidney disease, and nonalcoholic fatty liver disease (NAFLD). Herein we begin to address this issue by revealing phenotypic and metabolic responses to diet-induced obesity (DIO) in a side-by-side male vs. female C57BL/6J study. Beginning at 6 weeks of age, mice were exposed to either an obesogenic diet (60% calories from fat) or control diet (10% calories from fat) for 19 weeks. Similar to numerous reported observations with the 60% diet, male mice experienced significant weight gain over time, elevated fasting blood glucose, impaired glucose tolerance and significantly elevated circulating uric acid levels (2.54 ± 0.33 mg/dL) compared to age-matched lean male controls (1.53 ± 0.19 mg/dL). As expected, the female mice experienced a slower rate of weight gain compared to the males; however, they also developed elevated fasting blood glucose and impaired glucose tolerance compared to age-matched lean controls. Countervailing our previous report whereby the control diet for the female-only study was vivarium standard chow (18% calories from fat), the obese female mice did demonstrate significantly elevated circulating UA levels (2.55 ± 0.15 mg/dL) compared to the proper control (1.68 ± 0.12 mg/dL). This affirms that the choice of control diet is crucial for reaching durable conclusions. In toto, these results, for the first time, reveal elevated circulating UA to be a similar long-term response to obesogenic feeding for both males and females and mirrors clinical observations demonstrating hyperuricemia in obesity for both sexes. Full article

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

Gout is a prevalent form of inflammatory arthritis caused by the crystallization of uric acid in the joints and soft tissues, leading to acute, painful attacks. Activation of the NLRP3 inflammasome in mononuclear cells, along with inflammasome-independent pathways, is responsible for the inflammatory phenotype in gout. Research into the different aspects of gout pathophysiology and potential treatment options is ongoing. This review highlights some of the basic research published in the 12 months following the 2022 Gout, Hyperuricemia, and Crystal-Associated Disease Network (G-CAN) conference and focuses on mechanisms of inflammation, encompassing pro- and anti-inflammatory pathways, as well as the exploration of various biological systems, such as single-cell transcriptomics, proteomics, metabolomics, and microbiome analyses. Full article