Basic calcium phosphate crystals and osteoarthritis pathogenesis

Stack, John; McCarthy, Géraldine

doi:10.1097/bor.0000000000000245

Cited by 39 publications

(18 citation statements)

References 24 publications

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“…A large body of evidence supports the idea that calciumcontaining crystals are active players in the initiation and progression of OA [5,9,37,38]. However, the mechanisms of cartilage calcification are largely unknown and to date, there is no treatment that can prevent crystal deposition or dissolve already formed calcifications.…”

Section: Discussionmentioning

confidence: 99%

The protective role of the 3-mercaptopyruvate sulfurtransferase (3-MST)-hydrogen sulfide (H2S) pathway against experimental osteoarthritis

et al. 2020

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Background: Osteoarthritis (OA) is characterized by the formation and deposition of calcium-containing crystals in joint tissues, but the underlying mechanisms are poorly understood. The gasotransmitter hydrogen sulfide (H 2 S) has been implicated in mineralization but has never been studied in OA. Here, we investigated the role of the H 2 Sproducing enzyme 3-mercaptopyruvate sulfurtransferase (3-MST) in cartilage calcification and OA development. Methods: 3-MST expression was analyzed in cartilage from patients with different OA degrees, and in cartilage stimulated with hydroxyapatite (HA) crystals. The modulation of 3-MST expression in vivo was studied in the meniscectomy (MNX) model of murine OA, by comparing sham-operated to MNX knee cartilage. The role of 3-MST was investigated by quantifying joint calcification and cartilage degradation in WT and 3-MST −/− meniscectomized knees. Chondrocyte mineralization in vitro was measured in WT and 3-MST −/− cells. Finally, the effect of oxidative stress on 3-MST expression and chondrocyte mineralization was investigated. Results: 3-MST expression in human cartilage negatively correlated with calcification and OA severity, and diminished upon HA stimulation. In accordance, cartilage from menisectomized OA knees revealed decreased 3-MST if compared to sham-operated healthy knees. Moreover, 3-MST −/− mice showed exacerbated joint calcification and OA severity if compared to WT mice. In vitro, genetic or pharmacologic inhibition of 3-MST in chondrocytes resulted in enhanced mineralization and IL-6 secretion. Finally, oxidative stress decreased 3-MST expression and increased chondrocyte mineralization, maybe via induction of pro-mineralizing genes. Conclusion: 3-MST-generated H 2 S protects against joint calcification and experimental OA. Enhancing H 2 S production in chondrocytes may represent a potential disease modifier to treat OA.

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Section: Discussionmentioning

confidence: 99%

The protective role of the 3-mercaptopyruvate sulfurtransferase (3-MST)-hydrogen sulfide (H2S) pathway against experimental osteoarthritis

et al. 2020

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“…Ca-Pi crystals have been known to act as mediators of inflammation in late stages of OA 18 . However, intra-articular injections of basic Ca-Pi crystals can induce OA-like changes 29 . In addition, Ca-Pi crystals have a positive feed forward loop with IL-6, which is an important mediator of joint damage as a key component of the senescence-associated secretory phenotype (SASP) 19 .…”

Section: Discussionmentioning

confidence: 99%

Calcium-phosphate complex increased during subchondral bone remodeling affects earlystage osteoarthritis

Jung

Han

Park

et al. 2018

Sci Rep

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An activation of osteoclasts and subchondral bone remodeling is a major histologic feature of early-stage osteoarthritis (OA), which can be accompanied by an increase of calcium (Ca) and phosphate (Pi) level in the subchondral milieu. Considering articular cartilage gets most of nutrition from subchondral bone by diffusion, these micro-environmental changes in subchondral bone can affect the physiology of articular chondrocytes. Here, we have shown that Ca is increased and co-localized with Pi in articular cartilage of early-stage OA. The Ca-Pi complex increased the production of MMP-3 and MMP-13 in the hypertrophic chondrocytes, which was dependent on nuclear factor-kappa B (NF-kB), p38 and extracellular signal-regulated kinase (Erk) 1/2 mitogen-activated protein (MAP) kinase and Signal transducer and activator of transcription 3 (STAT3) signaling. The Ca-Pi complexes increased the expression of endocytosis markers, and the inhibition of the formation of the Ca-Pi complex ameliorated the Ca-Pi complex-mediated increases of MMPs expression in hypertrophic chondrocytes. Our data provide insight regarding the Ca-Pi complex as a potential catabolic mediator in the subchondral milieu and support the pathogenic role of subchondral bone in the early stages of cartilage degeneration.

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“…В то же время бессимптомные и субклинические формы ПФА, такие как ОА с ПФА и бессимптомная форма, где явное активное кристалл-индуцированное воспаление отсутствует, интересуют ревматологов в аспекте возможного негативного влияния депонирования кристаллов на структурное прогрессирование ОА [6,7]. Хотя у многих больных ОА с явлениями хондрокальциноза степень выраженности структурных изменений хряща и субхондральной кости минимальна, во многих работах (в основном, экспериментальных) было показано, что отложение кристаллов ПФК и ОФК в патологически модифицированный хрящ у больных ОА может индуцировать низкоуровневое воспаление СО за счет индукции синтеза хондроцитами, фибробластами и синовиоцитами оксида азота, простагландинов, провоспалительных цитокинов, включая интерлейкин 1 (ИЛ1) и ИЛ6, и повышения экспрессии матриксных металлопротеиназ [8][9][10][11][12]. Кристаллы солей также могут оказывать влияние на функции остеобластов и остеокластов, способствуя локальной резорбции и ремоделированию субхондральной кости [12,13].…”

Section: Discussionunclassified

Assessment of clinical significance of ultrasonographic detection ofhyperechogenic deposits in hyaline cartilage in patients with knee osteoarthritis

Петров

Matveeva

Petrov

2019

Naučno-praktičeskaâ revmatologiâ

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The aimof the study was to assess the relationship between the detection of hyperechogenic deposits (HD) in the hyaline cartilage of the knee joints (KJ) at ultrasonography in patients with osteoarthritis (OA), clinical manifestations and structural changes according to KJ ultrasonography and radiography.Material and methods.A prospective analysis of clinical, radiological and ultrasonographic data of 114 patients with knee OA was conducted. The patients were divided into two groups: 32 patients with HD detected in at least one of the KJ, and 82 patients without HD; 32 patients of the 1st group and 34 patients of the 2nd group were observed for 2 years. A comparative assessment of initial clinical manifestations (WOMAC index), x-ray data and ultrasonographic parameters of the subchondral bone, hyaline cartilage and the degree of synovial inflammation in the groups of patients at the beginning of the study and after 2 years was carried out. The exclusion criteria were other joint diseases; paroxysmal course of the inflammatory process in KJ; trauma and history of operations on KJ; ESR >20 mm/h, uric acid level >360 μmol/l and C-reactive protein >5 mg/l.Results and discussion.HD in hyaline cartilage was found in 28.1% of patients with knee OA. After 2 years HD remained in all patients having them at inclusion, and in 5.6% of the patients they were found for the first time. In 13 patients with HD in hyaline cartilage, synovial fluid was studied and in all cases calcium pyrophosphate crystals were identified by phase-contrast microscopy. The presence of HD in the hyaline cartilage of patients with knee OA was accompanied by more pronounced ultrasonographic signs of synovitis and was associated with a higher rate of osteophytes growth in the absence of the changes of the hyaline cartilage thickness according to the ultrasonography and the width of the joint space according to x-ray.Conclusion.The presence of HD in the hyaline cartilage of patients with knee OA according to ultrasound examination may be associated with the deposition of calcium pyrophosphate crystals and is associated with persistent synovitis and accelerated growth of osteophytes.

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Basic calcium phosphate crystals and osteoarthritis pathogenesis

Abstract: BCP crystals can activate a number of inflammatory pathways which in turn may lead to cartilage degradation and osteoarthritis. Understanding of these pathways may ultimately yield targeted therapies for osteoarthritis, for which none currently exists.

Cited by 39 publications

References 24 publications

The protective role of the 3-mercaptopyruvate sulfurtransferase (3-MST)-hydrogen sulfide (H2S) pathway against experimental osteoarthritis

The protective role of the 3-mercaptopyruvate sulfurtransferase (3-MST)-hydrogen sulfide (H2S) pathway against experimental osteoarthritis

Calcium-phosphate complex increased during subchondral bone remodeling affects earlystage osteoarthritis

Assessment of clinical significance of ultrasonographic detection ofhyperechogenic deposits in hyaline cartilage in patients with knee osteoarthritis

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