Morphology and physiology of the epiphyseal growth plate.

Abstract

Mammalian growth plate, also known as epiphyseal plate or physis, is highly specialized mesodermderived cartilaginous structure. It develops in the bone bud, secondary to presence of the primary ossification centers and is responsible for bone elongation. The plates are formed by numerous cells that rapidly divide and mature. Post puberty, the epiphyseal cartilage cell division decreases, bone completely replaces cartilage, and the epiphyseal plates fuse together with primary and secondary ossification centers [1,2]. Cartilage differentiation processPresently, four major stages of chondrocyte differentiation are known, i.a., mesenchymal precursor cells (MPCs), prechondrocytes, early chondroblasts and terminally differentiated chondrocytes [1][2][3][4]. Abstract: The epiphyseal growth plate develops from the cartilaginous-orientated mesenchymal cells that express SOX family genes. This multilayer structure is formed by the proliferation and hypertrophy of cells that synthesize the extracellular matrix composed of collagen (mainly type II, IX, X, XI) and proteoglycans (aggrecan, decorin, annexin II, V and VI). The resting zone is responsible for protein synthesis and maintaining a germinal structure. In the proliferative zone, cells rapidly duplicate. The subsequent morphological changes take place in the transformation zone, divided into the upper and lower hypertrophic layers. In the degenerative zone, the mineralization process becomes intensive due to increased release of alkaline phosphate, calcium and matrix vesicles by terminally differentiated chondrocytes and some other factors e.g., metaphyseal ingrowth vessels. At this level, as well as in the primary and secondary spongiosa zones, chondrocytes undergo apoptosis and are physiologically eliminated. Unlike adult cartilage, in fetal and early formed growth plates, unusual forms such as autophagal bodies, paralysis and dark chondrocytes are also observed. Their ultrastructure differs greatly from apoptotic and normal cartilage cells. Chondrocyte proliferation and differentiation are regulated by various endocrine, paracrine, and autocrine agents such as growth, thyroid and sex hormones, beta-catenin, bone morphogenetic proteins, insulin-like growth factor, iodothyronine deiodinase, leptin, nitric oxide, transforming growth factor beta and vitamin D metabolites. However, the most significant factor is parathyroid hormone-related protein (PTHrP) which is synthesized in the perichondrium by terminally differentiated chondrocytes. Secondary to activation of PTH/PTHrP receptors, PTHrP stimulates cell proliferation by G protein activation and delays their transformation into prehypertrophic and hypertrophic chondrocytes. When proliferation is completed, chondrocytes release Indian hedgehog (Ihh), which stimulates PTHrP synthesis via a feedback loop. Any disturbances of the epiphyseal development and its physiology result in various skeletal abnormalities known as dysplasia.

The emerging roles of ADAMTS-7 and ADAMTS-12 matrix metalloproteinases

“…[83][84][85] IHH is expressed at the prehypertrophic-hypertrophic boundary. Since PTHrP, ADAMTS-7, and ADAMTS-12 all function as negative regulators of chondrogenesis, these molecules have the potential to function within the same regulatory pathway.…”

Ellis–van Creveld Syndrome in Grey Alpine Cattle

“…17 Maturation of chondrocytes occurs due to physical and biochemical changes that occur in a spatial and temporal pattern. 4 The role of type X collagen is to facilitate the deposition of calcium within the matrix. 1 As hypertrophic chondrocytes become terminally differentiated, the gene Col10a1, which encodes for collagen X, ceases to be expressed in chondrocytes, leading to activation of a group of genes that induce extracellular matrix mineralization and cellular apoptosis.…”

“…1 As hypertrophic chondrocytes become terminally differentiated, the gene Col10a1, which encodes for collagen X, ceases to be expressed in chondrocytes, leading to activation of a group of genes that induce extracellular matrix mineralization and cellular apoptosis. 4 Collagen X and cellular hypertrophy together are indicators of terminally differentiated growth plate chondrocytes. 4 Collagen X is distributed in the hypertrophic zone of the fetal physis, around blood vessels, and in the perichondrium.…”

“…13 Collagen X is primarily found in the hypertrophic zone, and its role is to facilitate the deposition of calcium within the matrix. 4 Therefore, collagen II can be used as a marker of cartilage matrix formation and collagen X as a marker of chondrocyte hypertrophy. 22 Fibroblast growth factor (FGF) signaling is essential for endochondral bone formation.…”

Current Applications of Mesenchymal Stem Cells for Cartilage Tissue Engineering

“…Cartilage formation begins by the condensation and then the diferentiation of MSCs to prechondrocytes; thus, the cells irst express types I and IIA collagen, and begins to synthesize GAGs and adhesion-related proteins such as cadherin [68]. This cascade of events is in response to the efect of factors, such as some members of the TGF-β superfamily (TGF-β1, -β2, and -β3), which are able to induce the synthesis of ibronectin, tenascin, and syndecan [69].…”