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Published on: August 22, 2016
Mineralization/anti-mineralization networks in the skin and vascular connective tissues
1Department of Dermatology and Cutaneous Biology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Abstract:
Ectopic mineralization has been linked to several common clinical conditions with considerable morbidity and mortality. The mineralization processes, both metastatic and dystrophic, affect the skin and vascular connective tissues. There are several contributing metabolic and environmental factors that make uncovering of the precise pathomechanisms of these acquired disorders exceedingly difficult. Several relatively rare heritable disorders share phenotypic manifestations similar to those in common conditions, and, consequently, they serve as genetically controlled model systems to study the details of the mineralization process in peripheral tissues. This overview will highlight diseases with mineral deposition in the skin and vascular connective tissues, as exemplified by familial tumoral calcinosis, pseudoxanthoma elasticum, generalized arterial calcification of infancy, and arterial calcification due to CD73 deficiency. These diseases, and their corresponding mouse models, provide insight into the pathomechanisms of soft tissue mineralization and point to the existence of intricate mineralization/anti-mineralization networks in these tissues. This information is critical for understanding the pathomechanistic details of different mineralization disorders, and it has provided the perspective to develop pharmacological approaches to counteract the consequences of ectopic mineralization.
Insights
Ectopic mineralization in skin and blood vessels causes disease. Rare genetic disorders, like familial tumoral calcinosis, model these conditions, revealing complex networks that may offer new treatment targets.
Area of Science:
- Pathology
- Genetics
- Biochemistry
Background:
- Ectopic mineralization, affecting skin and vascular tissues, contributes to significant morbidity and mortality.
- Metabolic and environmental factors complicate understanding the precise pathomechanisms of acquired mineralization disorders.
- Rare heritable disorders with similar phenotypes serve as valuable genetic models for studying peripheral tissue mineralization.
Purpose of the Study:
- To review diseases involving mineral deposition in skin and vascular connective tissues.
- To highlight familial tumoral calcinosis, pseudoxanthoma elasticum, generalized arterial calcification of infancy, and CD73-deficiency-related arterial calcification.
- To discuss insights gained from these diseases and their mouse models into soft tissue mineralization.
Main Methods:
- Literature review of ectopic mineralization disorders.
- Analysis of genetic models for soft tissue calcification.
- Examination of mineralization and anti-mineralization networks.
Main Results:
- Familial tumoral calcinosis, pseudoxanthoma elasticum, GACI, and CD73 deficiency exemplify soft tissue mineralization disorders.
- These conditions and their mouse models offer insights into pathomechanisms of ectopic mineralization.
- Evidence suggests intricate mineralization/anti-mineralization networks exist in affected tissues.
Conclusions:
- Studying rare genetic disorders provides critical insights into common ectopic mineralization diseases.
- Understanding these pathomechanisms is key for developing targeted pharmacological interventions.
- Identifying mineralization/anti-mineralization networks opens avenues for treating ectopic mineralization consequences.
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