Role of OSCAR Signaling in Osteoclastogenesis and Bone Disease

Nedeva, Iva R.; Vitale, Mattia; Elson, Ari; Hoyland, Judith A.; Bella, Jordi

doi:10.3389/fcell.2021.641162

Cited by 40 publications

(37 citation statements)

References 124 publications

(246 reference statements)

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“…Moreover, qRT-PCR was also used to confirm the expression of TRAP when cells were cultured on Fmoc-FF/S/RGD with incorporated Hap. Indeed, since the OC-commitment it is known to begin around days 2–3 [5] , we compared the expression of TRAP at day 7 with that at day 3 and we successfully demonstrated that there was a significant increased expression of TRAP at day 7 ( Fig. 6 E ), confirming the OC-differentiation of Raw 264.7 cells cultured on Fmoc-FF/S/RGD with incorporated Hap.…”

Section: Resultsmentioning

confidence: 53%

“…Bone is a highly dynamic and hierarchically organised organ, consisting of a complex network of cells embedded in a 3D structure of organic-inorganic nanocomposite, which confers remarkable mechanical performance, including high strength and fracture toughness [ 1 , 2 ]. Bone is constantly self-renewing through a finely regulated balance of two processes: osteoclastogenesis, through bone-resorbing osteoclasts (OCs), and osteoblastogenesis through bone-forming osteoblasts (OBs) [3] , [4] , [5] . Disruption of the equilibrium between these processes can cause bone defects or may lead to increased risk of bone fractures [6] .…”

Section: Introductionmentioning

confidence: 99%

“…Disruption of the equilibrium between these processes can cause bone defects or may lead to increased risk of bone fractures [6] . OCs are hematopoietically-derived multinucleated cells that play an essential role in maintaining bone turnover and they are key players in bone diseases, such as osteoporosis and different forms of cancer [ 5 , 7 , 8 ]. Bone tissue engineering can provide useful tools to mimic the natural bone microenvironment and study the mechanisms involved in bone diseases.…”

Section: Introductionmentioning

confidence: 99%

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Hydroxyapatite-decorated Fmoc-hydrogel as a bone-mimicking substrate for osteoclast differentiation and culture

et al. 2022

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Hydrogels are water-swollen networks with great potential for tissue engineering applications. However, their use in bone regeneration is often hampered due to a lack of materials’ mineralization and poor mechanical properties. Moreover, most studies are focused on osteoblasts (OBs) for bone formation, while osteoclasts (OCs), cells involved in bone resorption, are often overlooked. Yet, the role of OCs is pivotal for bone homeostasis and aberrant OC activity has been reported in several pathological diseases, such as osteoporosis and bone cancer. For these reasons, the aim of this work is to develop customised, reinforced hydrogels to be used as material platform to study cell function, cell-material interactions and ultimately to provide a substrate for OC differentiation and culture. Here, Fmoc-based RGD-functionalised peptide hydrogels have been modified with hydroxyapatite nanopowder (Hap) as nanofiller, to create nanocomposite hydrogels. Atomic force microscopy showed that Hap nanoparticles decorate the peptide nanofibres with a repeating pattern, resulting in stiffer hydrogels with improved mechanical properties compared to Hap- and RGD-free controls. Furthermore, these nanocomposites supported adhesion of Raw 264.7 macrophages and their differentiation in 2D to mature OCs, as defined by the adoption of a typical OC morphology (presence of an actin ring, multinucleation, and ruffled plasma membrane). Finally, after 7 days of culture OCs showed an increased expression of TRAP, a typical OC differentiation marker. Collectively, the results suggest that the Hap/Fmoc-RGD hydrogel has a potential for bone tissue engineering, as a 2D model to study impairment or upregulation of OC differentiation. Statement of significance Altered osteoclasts (OC) function is one of the major cause of bone fracture in the most commonly skeletal disorders (e.g. osteoporosis). Peptide hydrogels can be used as a platform to mimic the bone microenvironment and provide a tool to assess OC differentiation and function. Moreover, hydrogels can incorporate different nanofillers to yield hybrid biomaterials with enhanced mechanical properties and improved cytocompatibility. Herein, Fmoc-based RGD-functionalised peptide hydrogels were decorated with hydroxyapatite (Hap) nanoparticles to generate a hydrogel with improved rheological properties. Furthermore, they are able to support osteoclastogenesis of Raw264.7 cells in vitro as confirmed by morphology changes and expression of OC-markers. Therefore, this Hap-decorated hydrogel can be used as a template to successfully differentiate OC and potentially study OC dysfunction.

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Section: Resultsmentioning

confidence: 53%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Hydroxyapatite-decorated Fmoc-hydrogel as a bone-mimicking substrate for osteoclast differentiation and culture

et al. 2022

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“…Osteoclast-associated receptor (OSCAR) is another collagenbinding receptor, which is expressed in osteoclasts in mice, and in monocytes, macrophages, dendritic cells, and osteoclasts in humans (148)(149)(150). It is a member of the leukocyte receptor complex that associates with FcRg, and through FcRg-signaling OSCAR is critical for osteoclastogenesis (150,151).…”

Section: Collagen-receptors Expressed By Macrophagesmentioning

confidence: 99%

Immune Modulatory Properties of Collagen in Cancer

2021

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During tumor growth the extracellular matrix (ECM) undergoes dramatic remodeling. The normal ECM is degraded and substituted with a tumor-specific ECM, which is often of higher collagen density and increased stiffness. The structure and collagen density of the tumor-specific ECM has been associated with poor prognosis in several types of cancer. However, the reason for this association is still largely unknown. Collagen can promote cancer cell growth and migration, but recent studies have shown that collagens can also affect the function and phenotype of various types of tumor-infiltrating immune cells such as tumor-associated macrophages (TAMs) and T cells. This suggests that tumor-associated collagen could have important immune modulatory functions within the tumor microenvironment, affecting cancer progression as well as the efficacy of cancer immunotherapy. The effects of tumor-associated collagen on immune cells could help explain why a high collagen density in tumors is often correlated with a poor prognosis. Knowledge about immune modulatory functions of collagen could potentially identify targets for improving current cancer therapies or for development of new treatments. In this review, the current knowledge about the ability of collagen to influence T cell activity will be summarized. This includes direct interactions with T cells as well as induction of immune suppressive activity in other immune cells such as macrophages. Additionally, the potential effects of collagen on the efficacy of cancer immunotherapy will be discussed.

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“…Роль мембранного белка Th17-лимфоцитов RANKL в патогенезе псориатического артрита состоит в его способности связываться с рецептором-активатором ядерного фактора-kB (RANK) на поверхности моноцитов/макрофагов субхондральной части кости и стимулировать их дифференцировку в остеокласты [4,13]. Кроме того, присутствующий на поверхности моноцитов остеокласт-ассоциированный рецептор (OSCAR) в присутствии TNF-α потенцирует действие RANKL, тем самым усиливая остеокластогенез [14]. Активированные остеокласты начинают секретировать ферменты деградации костного матрикса -тартрат-резистентную кислую фосфатазу (TRAP), матриксную металлопротеиназу 9 (MMP9) и катепсин К (CatK), которые подвергают резорбции минерализованную кость.…”

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Genetic markers for psoriatic arthritis in patients with psoriasis. Part I: non-HLA genes

Kubanov

Карамова

Чикин

et al. 2021

Vestnik dermatologii i venerologii

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Psoriatic arthritis often develops in patients with psoriasis and can lead to joint deformity, stiffness, dysfunction, and disability. Psoriatic arthritis is a polygenic disease. and the issue of personalizing the prognosis of its development can only be resolved taking into account the variability of plenty genomic loci associated with the development of the disease. The personification of the prognosis of the disease can be solved taking into account the variability of the set of genomic loci with which its development is associated. The review examines genomic polymorphisms associated with the development of psoriatic arthritis not psoriasis, except of HLA polymorphisms. Genome regions containing polymorphisms, allelic variants of which are associated both with the development of psoriatic arthritis and reducing the likelihood of its occurrence, are described. It has been reported that the predisposition to the development of psoriatic arthritis in patients with psoriasis is determined by genes encoding proteins involved in inflammation and bone metabolism.

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Role of OSCAR Signaling in Osteoclastogenesis and Bone Disease

Cited by 40 publications

References 124 publications

Hydroxyapatite-decorated Fmoc-hydrogel as a bone-mimicking substrate for osteoclast differentiation and culture

Hydroxyapatite-decorated Fmoc-hydrogel as a bone-mimicking substrate for osteoclast differentiation and culture

Immune Modulatory Properties of Collagen in Cancer

Genetic markers for psoriatic arthritis in patients with psoriasis. Part I: non-HLA genes

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