Apoptosis in the Extraosseous Calcification Process.

Federica Boraldi,Francesco Demetrio Lofaro,Daniela Quaglino

doi:10.3390/cells10010131

Federica Boraldi, Francesco Demetrio Lofaro + Show 1 more

Open Access

https://doi.org/10.3390/cells10010131

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Journal: Cells	Publication Date: Jan 12, 2021
Citations: 26	License type: CC BY 4.0

Affiliation: University of Modena and Reggio Emilia

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.

Highlights

Extraosseous calcification is a pathologic mineralization process occurring in soft connective tissues
This review aims to provide an overview of extraosseous calcification mechanisms focusing on the relationships between apoptosis and mineralization in cartilage and vascular tissues
Articular cartilage is typically composed of chondrocytes embedded within a rather amorphous extracellular matrix (ECM) comprised of collagen, different proteoglycans, structural proteins involved in cell-matrix and matrix-matrix interactions, proteinases and their inhibitors [108]

Summary

Extraosseous Calcification

Calcium (Ca2+ ) and inorganic phosphate (Pi) exceed their solubility in most tissues; calcification does not occur in soft connective tissues for the presence of circulating and local inhibitors [15]. When these regulatory mechanisms are skimpy, pathological mineralization overwhelms and takes place through active cellmediated processes partially overlapping those observed during skeletal formation. Minerals are mainly deposited as hydroxyapatite, in contrast, in soft connective tissues, crystals of different compositions have been described (Table 1)

Mitochondria and Oxidative Stress

Apoptosis and Cartilage Calcification

Extracellular Matrix Components in the Context of Cartilage Apoptosis

Death Receptors and Cytokines in the Context of Cartilage Apoptosis

Apoptosis and Vascular Calcification

Changes in Matrix Components in the Context of Vascular Apoptosis

Conclusions