Renal Pathophysiology
Manit Arya, Taimur T. Shah, Jas S. Kalsi, Herman S. Fernando, Iqbal S. Shergill, Asif Muneer, Hashim U. Ahmed in MCQs for the FRCS(Urol) and Postgraduate Urology Examinations, 2020
Tamm-Horsfall protein, which is the most abundant urinary protein, is secreted by renal epithelial cells in the thick ascending limb and the distal convoluted tubule as a membrane-anchored protein. It is a potent inhibitor of calcium oxalate monohydrate crystal aggregation, but not growth. Nephrocalcin, an acidic glycoprotein, is synthesised in the proximal renal tubules and the thick ascending limb. Osteopontin, or uropontin, is an acidic phosphorylated glycoprotein expressed in bone matrix and renal epithelial cells of the ascending limb of the loop of Henle and the distal tubule. Glycosaminoglycans, acid mucopolysaccharides, and RNA are examples of polyanions that have been shown to inhibit crystal nucleation and growth. The inhibitory activity of magnesium is derived from its complexation with oxalate, which reduces ionic oxalate concentration and calcium oxalate supersaturation. Among the glycosaminoglycans, heparin sulfate interacts most strongly with calcium oxalate monohydrate crystals.
The αv Integrins
Yoshikazu Takada in Integrins: The Biological Problems, 2017
Osteoclasts are derived from bone marrow precursor cells and migrate to bone where they subsequently fuse to form osteoclasts.30 A functional antigen, termed the osteoclast functional antigen (OFA), appears to be integrin αvβ3 and was identified on mature osteoclasts and their immediate precursors, but not on cells of the mononuclear phagocytic system.30In situ and in vitro studies have shown αvβ3 to be expressed by human, chick, and rat osteoclasts.30 Integrin αvβ3 was not expressed on osteoblasts or other bone marrow cells in situ by immunohistochemistry,30 although in vitro studies of osteosarcoma cell lines (which produce bone in situ) have demonstrated αvβ3 expression.1–3 Blocking antibodies directed toward integrin αvβ3 as well as RGD-containing peptides have resulted in osteoclast retraction or inhibition of bone resorption, and inhibition of osteoclast motility.30 Potential ligands for αvβ3 in bone include osteopontin, which contains an RGD peptide sequence.28,30 Osteopontin is synthesized by osteoblasts and has been identified adjacent to bone immediately prior to osteoclast invasion, by in situ hybridization.28,30 Taken together, these data suggest αvβ3 plays a role in osteoclast resorption of bone. Currently, several pharmaceutical firms are designing specific antagonists of the osteoclast αvβ3 to be used as potential inhibitors of osteoporosis.
Osteoimmunology in Aging
Shamim I. Ahmad in Aging: Exploring a Complex Phenomenon, 2017
Bone matrix provides support for bone cells but also exerts an essential role in bone homeostasis by releasing several molecules, including osteopontin, fibronectin, collagen, BSPs, and adhesion molecules, variously involved in the interaction between the bone cells and bone matrix [64]. Osteopontin increases bone resorption by inducing the expression of the osteoclastic immune receptor CD44, essential for cell migration, and by directly enhancing osteoclast attachment to bone extracellular matrix, required for the activation of osteoclast precursors. As a consequence of bone resorption, more osteoponin is further released from the extracellular matrix into the bone microenvironment and into the blood, thus amplifying local and systemic osteoclastogenesis [65].
Numerical investigation of the role of osteopontin on the mechanical strength of biological composites
Published in Computer Methods in Biomechanics and Biomedical Engineering, 2019
The basic building blocks in bone include hydroxyapatite minerals, collagen proteins and non-collagenous proteins such as osteopontin (Wegst and Ashby 2004; Dunlop and Fratzl 2010; Ji and Gao 2010; Launey et al. 2010; Wang and Gupta 2011). The focus of this paper is osteopontin. Osteopontin is an essential component in bone, and osteopontin-deficient bone was found to have lower fracture toughness (Thurner et al. 2010). Besides, osteopontin was also found to be crucial for the regulation of mineralisation (Hunter 2013; Holm et al. 2014; Foster et al. 2018) and high energy dissipation (Fantner et al. 2005; Fantner et al. 2007; Zappone et al. 2008). Previous studies also suggested that osteopontin acts as natural adhesive in biological materials (McKee and Nanci 1995, 1996a, 1996b; Nanci 1999; Fantner et al. 2005).
Roles of the bone marrow niche in hematopoiesis, leukemogenesis, and chemotherapy resistance in acute myeloid leukemia
Published in Hematology, 2018
Osteopontin (Opn) is an extracellular matrix glycoprotein secreted by endosteal osteoblasts. It plays a key role in cell dormancy, invasion and the development of MRD. Diverse receptors expressed on the cell surface can interact with Opn, including CD44 and various integrins, including α4β1, α5β1, α9β1, and others. The β3 integrins play a vital role in leukemogenesis and the chemoresistance of AML [72]. Retrospective studies have found a correlation between high levels of Opn expression and poor prognosis in AML patients [73,74]. Overexpression of Opn b and c isoforms led to angiopoiesis, and these isoforms might prevent the cell apoptosis induced by conventional chemotherapy in AML [75]. A bone marrow niche established an Opn-rich area can specifically recruit Opn-expressing blasts. In turn, leukemic cells secrete Opn into the niche. Opn regulation probably entails positive feedback through host-tumor cell interactions. Opn can also expand the quiescent microenvironment and endow leukemic blasts with resistance to chemotherapy. A blockade of the Opn signaling pathway markedly increased the proportion of cycling cells and inhibited cell homing, which ultimately led to a higher tumor load. Injection of anti-Opn into engrafted mice followed by treatment with Ara-C decreased the MRD burden compared with Ara-C chemotherapy alone. The Opn neutralizer-treated mice might be vulnerable to cytotoxic stresses [76].
Plasma osteopontin concentration is elevated in patients with coronary bare metal stent restenosis
Published in Acta Cardiologica, 2018
Kerem Can Yilmaz, Ugur Abbas Bal, Emir Karacaglar, Kaan Okyay, Alp Aydinalp, Aylin Yildirir, Haldun Muderrisoglu
Coronary stents are commonly used to treat occlusive coronary artery disease. Despite promising improvements in stent technology, the optimum treatment strategy for patients requiring coronary artery stenting is still not fully understood, particularly as it is not possible to predict which patients will develop in-stent restenosis. Neointimal hyperplasia of matrix and smooth muscle cells is a major cause of in-stent restenosis [1]. Osteopontin, a calcium-binding, phosphorylated glycoprotein and macrophage chemotactic protein, was originally identified as a mediator associated with bone remodelling and chronic inflammatory and autoimmune diseases but has subsequently been demonstrated to play an important role in the development of cardiovascular disease [2–4]. Osteopontin is a component of human atherosclerotic lesions, mainly secreted by monocytes/macrophages and to a lesser extent by endothelial and vascular smooth muscle cells [5]. It has also been reported that osteopontin plays a role in vascular remodelling and the development of athersclerosis [6–8]. Osteopontin regulates the proliferation of cultured rat vascular smooth muscle cells and human coronary artery smooth muscle cells in vitro [9,10]. A clinically significant association between plasma osteopontin concentration and atherosclerotic plaque formation has also been demonstrated, independent of the traditional cardiovascular risk factors. As cells responsible for neointimal proliferation release osteopontin, it has been proposed that higher plasma concentrations of osteopontin may be associated with in-stent restenosis.
Related Knowledge Centers
- Bone
- Exon
- Organic Compound
- Protein
- Glycoprotein
- Extracellular Matrix
- Osteoblast
- Sibling Proteins
- Base Pair
- Locus