Apoptosis in the Extraosseous Calcification Process

Abstract

Extraosseous calcification is a pathologic mineralization process occurring in soft connective tissues (e.g., skin, vessels, tendons, and cartilage). It can take place on a genetic basis or as a consequence of acquired chronic diseases. In this last case, the etiology is multifactorial, including both extra- and intracellular mechanisms, such as the formation of membrane vesicles (e.g., matrix vesicles and apoptotic bodies), mitochondrial alterations, and oxidative stress. This review is an overview of extraosseous calcification mechanisms focusing on the relationships between apoptosis and mineralization in cartilage and vascular tissues, as these are the two tissues mostly affected by a number of age-related diseases having a progressively increased impact in Western Countries.

Matrix Vesicles: Role in Bone Mineralization and Potential Use as Therapeutics

“…Whether these exosome-like MtVs could be identified upon release from their parent cell and how exactly they differ from the ectosome-like MtVs described earlier needs more detailed investigation. Vascular calcification [128] and Endochondral ossification [128,129,131] MtV, matrix vesicle; ALP, alkaline phosphatase; NNP, nucleotide pyrophosphatase; PS, phosphatidylserine; ACP, amorphous calcium phosphate; HAp, hydroxyapatite.…”

“…For example, in growth plates where terminally differentiated chondrocytes undergo apoptosis, this process results in the formation of ApoBDs [121]. This is also thought to be an important initiator of vascular calcification [128]. These ApoBDs are also able to accumulate calcium and phosphate, but they contain only a few calcium channel-forming annexins [121].…”

“…The concentration of the total MtV can be estimated by measuring the total protein content of the sample. This is often assessed by a bicinchoninic acid (BCA) protein assay [93,128,135]. Similar to other subtypes of EVs, MtVs carry transmembrane proteins such as CD9, CD63, and CD81 [25,26,136,139].…”

Bibliometric and Visual Analysis of Vascular Calcification Research

“…Through the potent combination of top keywords and literature, we attribute the research hotspots as follows: 1) The mechanism of VC in CKD or dialysis patients, including inflammation (Yuan et al, 2020), VSMC phenotype of osteogenic differentiation (Yang et al, 2020), overexpression of calcification-promoting factors (oxidative stress) (Watanabe et al, 2020), parathyroid hormone (Imafuku et al, 2020), fibroblast growth factor 23 (Jiang et al, 2020) as well as the suppression of calcification inhibitors (Liu et al, 2018); 2) various pathophysiological changes (atherosclerosis, arterial calcification, arterial stiffness, etc.) accompanied by CVD, and the impact of these changes on the prognosis of patients (Stabley and Towler, 2017;Mszar et al, 2020); 3) comparison of therapeutic effects between open valve replacement surgery and minimally invasive transcatheter valve replacement for aortic valve or heart valve stenosis (Ielasi et al, 2021); and 4) molecular and cellular mechanisms of VC, including various molecular signaling pathways and abnormal proliferation (Miyata et al, 2020) or apoptosis (Boraldi et al, 2021) of cells that regulate VC.…”

Programmed Cell Death in Health and Disease

“…Besides neurodegeneration, the dysregulation of apoptotic signaling pathways and excessive apoptosis are implicated in the development and progression of other pathological conditions such as parasitic and viral infection, and ectopic calcification, a pathological state that worsens the quality of life of aged patients by affecting the cardiovascular system (vessels and valves) and joints [ 8 ]. In their review, Boraldi et al [ 9 ] present an overview of ectopic calcification mechanisms in cartilage and vascular tissue, focusing on the interplay between apoptosis and mineralization. Notably, during extraosseus calcification, apoptotic bodies may function as nucleation sites for crystal deposition.…”