Barbara D. Boyan, Maryam Doroudi, Kayla Scott, Zvi Schwartz

Resultado de la investigación: Chapter

4 Citas (Scopus)


Cartilage is an avascular tissue characterized by cartilage cells surrounded by an extracellular matrix consisting primarily of type II collagen and proteoglycans with sulfated glycosaminoglycan side chains assembled into large aggregates. It is found in a number of anatomic locations, with modifications to meet the specific requirements for its function. Cartilage development is regulated by vitamin D metabolites, including 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3) and 24R,25-dihydroxyvitamin D3 (24R,25(OH)2D3). In the postfetal growth plate, 1α,25(OH)2D3 acts via the vitamin D receptor (VDR) to control chondrocyte maturation, tether formation, matrix metalloproteinase activity, and release of Ca++ into the extracellular matrix for calcification. VDR-null mice, which lack a functional VDR, develop an elongated hypertrophic cell zone, characteristic of rickets, demonstrating the importance of the VDR in growth plate maturation and calcification. In addition to traditional nuclear VDR-dependent signaling mechanisms, 1α,25(OH)2D3 acts through nongenomic mechanisms mediated by protein disulfide isomerase family A, member 3 to control phospholipase A2, phospholipase C, protein kinase C, and mitogen-activated protein kinase signaling, as well as by acting directly on extracellular matrix vesicles, releasing matrix proteases, and activating transforming growth factor beta stored in the matrix. The importance of 1α,25(OH)2D3 to growth plate maturation, calcification, and subsequent resorption by osteoclasts has been demonstrated by studies using mice in which Cyp27B1 has either been knocked out or using transgenic mice in which Cyp27B1 is overexpressed. 24R,25(OH)2D3 acts via phospholipase D and lysophosphatidic acid signaling to promote cell survival, inhibit apoptosis, and reduce inflammatory cytokine production. The relative contributions of these two vitamin D metabolites help to determine the rate and extent of cartilage maturation, particularly in the growth plate during endochondral ossification, but also in articular cartilage.

Idioma originalEnglish (US)
Título de la publicación alojadaBiochemistry, Physiology and Diagnostics
EditorialElsevier Inc.
Número de páginas13
ISBN (versión digital)9780128099667
ISBN (versión impresa)9780128099650
EstadoPublished - 2018

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)


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