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Crystalline Arthritis
Published in Jason Liebowitz, Philip Seo, David Hellmann, Michael Zeide, Clinical Innovation in Rheumatology, 2023
Other research focuses on a positive feedback loop between inflammation and pathologic calcification. Researchers from the University of Algarve, Portugal, hypothesize that vitamin K–dependent γ-carboxyglutamic acid–rich proteins (GRPs) are synthesized constitutively in human macrophages/monocytes and upregulated upon cellular activation. GRPs act both endogenously, decreasing the production of inflammatory mediators in macrophages/monocytes (e.g., TNFα, PGE2, IL-1β, NF-κB), and exogenously, when released into the extracellular tissues to coat BCP crystals and inhibit ECM calcification.73, 74 These processes are viable targets for potential therapeutic intervention in both BCP arthritis and osteoarthritis.
Calcium and Magnesium
Published in Luke R. Bucci, Nutrition Applied to Injury Rehabilitation and Sports Medicine, 2020
Routine outpatient assessment of calcium status is difficult. Calcium levels are maintained at the expense of skeletal reserves of calcium, so serum, plasma, and, usually, urinary calcium levels are not helpful indicators of calcium status. Rather, calcium status is most often determined by other factors that regulate calcium absorption, metabolism, and excretion. Current tests available on an outpatient basis include whole blood calcium level, blood cell calcium levels, serum vitamin D measurements (1,25OHD), urine γ-carboxyglutamic acid levels, parathyroid hormone (including C- and N-terminal portions), serum ionized calcium levels, urine calcium levels, hair calcium levels, bone mineral density, X-ray spectral analysis of buccal cells, and lymphocyte growth responses.600,705,713 No single determination is a valid indicator in all circumstances. Rather, a combination of several tests can give a picture of calcium status. As with other nutrients, it may be more clinically efficient and practical to initiate a trial of calcium supplementation and note clinical responses.
Phospholipids and the Clotting Process
Published in E. Nigel Harris, Thomas Exner, Graham R. V. Hughes, Ronald A. Asherson, Phospholipid-Binding Antibodies, 2020
Robert F. A. Zwaal, Edouard M. Bevers, Jan Rosing
Nelsestuen et al.46 measured with light scattering the dissociation constants for interaction of vitamin K-dependent coagulation factors with vesicles composed of 20 mol% phosphatidylserine and 80 mol% phosphatidylcholine (Table 2). Dissociation constants in the mi-cromolar range were found while affinity of the coagulation factors for these vesicles decreases in the order factor X-prothrombin-factor IX-factor VII. Activation of the coagulation factors has negligible effect on the binding affinity, presumably because this does not affect the amount of γ-carboxyglutamic acid residues in these proteins. Similar differences in affinity between the proteins can also be inferred from other binding studies,38,47-49 or from the effect of phospholipid vesicles on the kinetic parameters of prothrombin activation23,50 and factor X activation.51,53
Comparison of the Bone Regenerative Capacity of Three-Dimensional Uncalcined and Unsintered Hydroxyapatite/Poly-d /l -Lactide and Beta-Tricalcium Phosphate Used as Bone Graft Substitutes
Published in Journal of Investigative Surgery, 2021
Yunpeng Bai, Jingjing Sha, Takahiro Kanno, Kenichi Miyamoto, Katsumi Hideshima, Yumi Matsuzaki
The human OCN gene encodes bone γ-carboxyglutamic acid protein, a secreted protein produced primarily by osteoblasts [39]. Consequently, OCN is routinely used as a serum marker of well-differentiated osteoblastic bone formation and is thought to regulate mineralization within the bone matrix. During the bone-defect healing period, calcium granules first expand into the fracture containing callus chondrocytes and are then transported into the extracellular matrix (ECM), where they form the initial mineral deposits with phosphate [40]. During this process, soft callus is transformed into hard callus; generally, the peak of hard callus formation is reached by 14 days in animal models. This change can be defined not only by the histomorphometry of mineralized tissue but also by the detection of ECM markers such as OCN, type I procollagen, alkaline phosphatase, and osteonectin [30]. OCN is also considered an osteoblast-specific gene that is expressed during ossification, along with master transcriptional factors such as Runx2 and Osterix [41, 42]. During embryonic and postnatal bone development and fracture healing, intramembranous ossification consists mainly of osteogenic mesenchymal condensation and direct differentiation into osteoblasts, eventually producing bone [43, 44]. By contrast, the process of endochondral ossification is characterized not only by the differentiation of chondrocytes by mesenchymal condensation to form a cartilaginous template that is eventually replaced with bone but also by osteoblast cells that sometimes participate to form the bone collar, which subsequently becomes cortical bone [43].
Effects of bisphenol A and S on blood coagulation: in vivo, in vitro and in silico approaches in toxicodynamic
Published in Toxicology Mechanisms and Methods, 2021
Artur Paes Chagas, Beatriz Pereira Peixoto, Bianca Barros da Costa, Thamyris Almeida Moreira, Leonardo Paes Cinelli, Leandro Louback da Silva, Leandro Miranda-Alves, Clemilson Berto-Junior
Human FVII is a vitamin K-dependent factor with distinct subdomains: a gamma-carboxyglutamic acid-rich domain (GLA domain, from residue 1 to 38), a short hydrophobic domain (39–45), two epidermal growth factor (EGF)-like domain (47–84 and 85–131) and a C-terminal serine protease domain (from 153 to 406) (Vadivel and Bajaj 2012). It may be activated by other coagulation factors such as FXa, FIXa and FVIIa, which in turns lead to a cleavage between ARG152 and ILE153, activating the enzyme (Prasad and Sen 2018). It becomes necessary to measure how much BPA and BPS can interact with activated FVII. Therefore, in silico approach rises as a great opportunity to explore interaction between FVIIa and bisphenols, although, as the in vivo assay was performed in zebrafish and in vitro assays were performed in human samples, an alignment should be performed first to help validating our findings. Alignment displayed a relatively low identity (49%) and high gaps (211) which could be explained by the use of only the heavy chain of human FVIIa and the entire zebrafish protein, since this was the portion used for docking experiments and was available for human (https://www.ncbi.nlm.nih.gov/protein/1JBU_H) but not for zebrafish in NCBI website. However, the same amino acids residues required for redocking validation and for docking studies were present at the same position in zebrafish and human sequences: position 236(H) is HIS57, 381(D) is ASP189, 382(S) is SER190, 387(S) is SER195, 406(S) is SER214, 407(W) is TRP215, 410(G) is GLY219 and 411(C) is CYS220 [22], which encouraged us to step to docking simulations.
Circulating Levels of Osteoprotegerin, Osteocalcin and Osteopontin in Patients with Rheumatoid Arthritis: A Systematic Review and Meta-Analysis
Published in Immunological Investigations, 2019
Li-Na Liu, Yan-Mei Mao, Chan-Na Zhao, Hong Wang, Fei-Fei Yuan, Xiao-Mei Li, Hai-Feng Pan
The OCN found in serum comes from new cellular synthesis rather than from the release of bone matrix protein during bone resorption and it contains three residues of glutamic acid, which are carboxylated to form carboxyglutamic acid (James et al., 1979; Price et al., 1981). Degradation of bone may depend on OCN content in the matrix: the GLA-containing proteins have chemotactic activity on macrophages and monocytes (Lian et al., 1986). It may be a growth and differentiation factor for the progenitor-cells accelerating bone resorption and may decide the activation of bone resorbing cells (Lian et al., 1986; Magaro et al., 1989). The synovial fluid levels of OCN were usually less than serum concentrations, but in two RA and four OA patients, the ratio was opposite (Campion et al., 1989). The serum OCN levels have no significant between RA and OA in Fairney et al. and Wei et al. (Angela Fairney et al., 1990; Wei et al., 2016).