Histologic and ultrastructural studies on the mineralization process in hypophosphatasia
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Infantile hypophosphatasia impairs cartilage mineralization due to alkaline phosphatase deficiency, affecting chondrocytes and matrix. However, bone mineralization not mediated by matrix vesicles remains normal.
Area of Science:
- Pediatric Endocrinology
- Skeletal Biology
- Biochemistry
Background:
- Infantile hypophosphatasia (HPP) is a severe genetic disorder characterized by defective bone mineralization.
- The role of alkaline phosphatase in cartilage and bone mineralization is critical but not fully understood in HPP.
Purpose of the Study:
- To investigate the ultrastructural and histochemical changes in chondroosseous tissue of infants with HPP.
- To elucidate the specific mechanisms of impaired mineralization in HPP.
Main Methods:
- Light, transmission, and scanning electron microscopy of chondroosseous tissue from HPP and control infants.
- Alkaline phosphatase histochemical staining of growth plate cartilage.
- Analysis of chondrocytes, matrix vesicles, and crystal formation.
Main Results:
- Reduced alkaline phosphatase activity in the growth plate of HPP infants.
- Increased hypertrophic chondrocytes and persistent cartilage islets in the metaphysis.
- Matrix vesicles present but with reduced mineralization; impaired crystal formation and orientation in calcifying cartilage and newly formed bone.
Conclusions:
- Impaired cartilage mineralization in HPP is primarily due to alkaline phosphatase deficiency.
- Matrix vesicles are present in HPP, but their function is compromised.
- Secondary bone mineralization, independent of matrix vesicles, is unaffected in HPP.
Abstract:
Chondroosseous tissue from six infants with infantile hypophosphatasia and six control infants were studied by light, transmission, and scanning electron microscopy. Alkaline phosphatase histochemical reaction of the growth plate was studied in two infants and was greatly reduced when compared to two control infants. Hypertrophic chondrocytes were increased in number with persisting cartilage islets in the metaphysis. In five of the six cases studied, chondrocytes and intercartilagenous intercellular chondroid matrix appeared ultrastructurally normal. Matrix vesicle distribution was similar to that of control subjects, but they were associated with few mineral crystals. In two infants, the matrix vesicles were alkaline phosphatase nonreactive. In the calcifying zone of the growth plate and in the newly formed metaphyseal trabecular bone, cartilagenous calcospherites often were small and the orientation of crystals was nonradial when compared to that of control infants. The mineralization of diaphyseal bone appeared normal. It seems that matrix vesicles are present in hypophosphatasia and that the impaired mineralization of cartilage is due primarily to the deficiency of alkaline phosphatase. In spite of the lack of alkaline phosphatase, secondary mineralization of bone which is not mediated by matrix vesicles was normal.