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Perlecan maintains the integrity of cartilage and some basement membranes.

Costell M, Gustafsson E, Aszódi A, Mörgelin M, Bloch W, Hunziker E, Addicks K, Timpl R, Fässler R - J. Cell Biol. (1999)

Bottom Line: As a consequence, small clefts are formed in the cardiac muscle leading to blood leakage into the pericardial cavity and an arrest of heart function.The defects in the BM separating the brain from the adjacent mesenchyme caused invasion of brain tissue into the overlaying ectoderm leading to abnormal expansion of neuroepithelium, neuronal ectopias, and exencephaly.Finally, homozygotes developed a severe defect in cartilage, a tissue that lacks BMs. The chondrodysplasia is characterized by a reduction of the fibrillar collagen network, shortened collagen fibers, and elevated expression of cartilage extracellular matrix genes, suggesting that perlecan protects cartilage extracellular matrix from degradation.

View Article: PubMed Central - PubMed

Affiliation: Department of Experimental Pathology, Lund University, S-221 85 Lund, Sweden.

ABSTRACT
Perlecan is a heparan sulfate proteoglycan that is expressed in all basement membranes (BMs), in cartilage, and several other mesenchymal tissues during development. Perlecan binds growth factors and interacts with various extracellular matrix proteins and cell adhesion molecules. Homozygous mice with a mutation in the perlecan gene exhibit normal formation of BMs. However, BMs deteriorate in regions with increased mechanical stress such as the contracting myocardium and the expanding brain vesicles showing that perlecan is crucial for maintaining BM integrity. As a consequence, small clefts are formed in the cardiac muscle leading to blood leakage into the pericardial cavity and an arrest of heart function. The defects in the BM separating the brain from the adjacent mesenchyme caused invasion of brain tissue into the overlaying ectoderm leading to abnormal expansion of neuroepithelium, neuronal ectopias, and exencephaly. Finally, homozygotes developed a severe defect in cartilage, a tissue that lacks BMs. The chondrodysplasia is characterized by a reduction of the fibrillar collagen network, shortened collagen fibers, and elevated expression of cartilage extracellular matrix genes, suggesting that perlecan protects cartilage extracellular matrix from degradation.

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Ultrastructure of hypertrophic chondrocytes and territorial matrix. (A and C) The hypertrophic chondrocyte in a normal mouse femur has low organelle density. The septa are homogeneously filled with fibrillar collagen (arrows) and calcified material (c). (B and D) The hypertrophic chondrocyte in a perlecan- femur displays increased density of organelles, and the cytosol is highly enriched with free ribosomes and polysomes (arrowheads). The adjacent pericellular matrix compartment is filled with fibrillar collagen but lacks calcification. (E and F) The territorial zone in normal cartilage shows random distribution of collagen fibrils. The collagen fibrils are of uniform diameter and length (E). The territorial zone in homozygotes lacks a well organized collagen fibrillar network. The collagen fibrils are shorter in length, lower in contrast, and the density is reduced. (G) The expression of Col2a1, matrilin-3, and COMP mRNA is increased in perlecan-deficient cartilage. Abbreviations: P, plasma membrane; N, cell nucleus; and C, calcification. Bars: (A and B) 5 μm; 1 μm (C and D); and (E and F) 0.5 μm.
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Figure 8: Ultrastructure of hypertrophic chondrocytes and territorial matrix. (A and C) The hypertrophic chondrocyte in a normal mouse femur has low organelle density. The septa are homogeneously filled with fibrillar collagen (arrows) and calcified material (c). (B and D) The hypertrophic chondrocyte in a perlecan- femur displays increased density of organelles, and the cytosol is highly enriched with free ribosomes and polysomes (arrowheads). The adjacent pericellular matrix compartment is filled with fibrillar collagen but lacks calcification. (E and F) The territorial zone in normal cartilage shows random distribution of collagen fibrils. The collagen fibrils are of uniform diameter and length (E). The territorial zone in homozygotes lacks a well organized collagen fibrillar network. The collagen fibrils are shorter in length, lower in contrast, and the density is reduced. (G) The expression of Col2a1, matrilin-3, and COMP mRNA is increased in perlecan-deficient cartilage. Abbreviations: P, plasma membrane; N, cell nucleus; and C, calcification. Bars: (A and B) 5 μm; 1 μm (C and D); and (E and F) 0.5 μm.

Mentions: The ultrastructure of cartilage tissue derived from an E17.5 limb showed that wild-type hypertrophic chondrocytes were electron lucent with a paucity of organelles in the cytosol (Fig. 8A and Fig. C). The wild-type chondrocytes also showed contacts with the surrounding matrix that was homogeneously filled with fibrillar collagen (Fig. 8 A). In contrast, hypertrophic chondrocytes of perlecan- mice displayed an increased density of organelles and distended cisternae of ER (Fig. 8B and Fig. D). The cytosol was enriched with free ribosomes and polysomes (Fig. 8 D, arrowheads). The collagen fibrils in wild-type growth plate cartilage showed a random distribution, had uniform length and diameter, and formed a typical network (Fig. 8 E). The perlecan- growth plate cartilage lacked such collagen network and the fibrils were shorter in length (Fig. 8 F).


Perlecan maintains the integrity of cartilage and some basement membranes.

Costell M, Gustafsson E, Aszódi A, Mörgelin M, Bloch W, Hunziker E, Addicks K, Timpl R, Fässler R - J. Cell Biol. (1999)

Ultrastructure of hypertrophic chondrocytes and territorial matrix. (A and C) The hypertrophic chondrocyte in a normal mouse femur has low organelle density. The septa are homogeneously filled with fibrillar collagen (arrows) and calcified material (c). (B and D) The hypertrophic chondrocyte in a perlecan- femur displays increased density of organelles, and the cytosol is highly enriched with free ribosomes and polysomes (arrowheads). The adjacent pericellular matrix compartment is filled with fibrillar collagen but lacks calcification. (E and F) The territorial zone in normal cartilage shows random distribution of collagen fibrils. The collagen fibrils are of uniform diameter and length (E). The territorial zone in homozygotes lacks a well organized collagen fibrillar network. The collagen fibrils are shorter in length, lower in contrast, and the density is reduced. (G) The expression of Col2a1, matrilin-3, and COMP mRNA is increased in perlecan-deficient cartilage. Abbreviations: P, plasma membrane; N, cell nucleus; and C, calcification. Bars: (A and B) 5 μm; 1 μm (C and D); and (E and F) 0.5 μm.
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Figure 8: Ultrastructure of hypertrophic chondrocytes and territorial matrix. (A and C) The hypertrophic chondrocyte in a normal mouse femur has low organelle density. The septa are homogeneously filled with fibrillar collagen (arrows) and calcified material (c). (B and D) The hypertrophic chondrocyte in a perlecan- femur displays increased density of organelles, and the cytosol is highly enriched with free ribosomes and polysomes (arrowheads). The adjacent pericellular matrix compartment is filled with fibrillar collagen but lacks calcification. (E and F) The territorial zone in normal cartilage shows random distribution of collagen fibrils. The collagen fibrils are of uniform diameter and length (E). The territorial zone in homozygotes lacks a well organized collagen fibrillar network. The collagen fibrils are shorter in length, lower in contrast, and the density is reduced. (G) The expression of Col2a1, matrilin-3, and COMP mRNA is increased in perlecan-deficient cartilage. Abbreviations: P, plasma membrane; N, cell nucleus; and C, calcification. Bars: (A and B) 5 μm; 1 μm (C and D); and (E and F) 0.5 μm.
Mentions: The ultrastructure of cartilage tissue derived from an E17.5 limb showed that wild-type hypertrophic chondrocytes were electron lucent with a paucity of organelles in the cytosol (Fig. 8A and Fig. C). The wild-type chondrocytes also showed contacts with the surrounding matrix that was homogeneously filled with fibrillar collagen (Fig. 8 A). In contrast, hypertrophic chondrocytes of perlecan- mice displayed an increased density of organelles and distended cisternae of ER (Fig. 8B and Fig. D). The cytosol was enriched with free ribosomes and polysomes (Fig. 8 D, arrowheads). The collagen fibrils in wild-type growth plate cartilage showed a random distribution, had uniform length and diameter, and formed a typical network (Fig. 8 E). The perlecan- growth plate cartilage lacked such collagen network and the fibrils were shorter in length (Fig. 8 F).

Bottom Line: As a consequence, small clefts are formed in the cardiac muscle leading to blood leakage into the pericardial cavity and an arrest of heart function.The defects in the BM separating the brain from the adjacent mesenchyme caused invasion of brain tissue into the overlaying ectoderm leading to abnormal expansion of neuroepithelium, neuronal ectopias, and exencephaly.Finally, homozygotes developed a severe defect in cartilage, a tissue that lacks BMs. The chondrodysplasia is characterized by a reduction of the fibrillar collagen network, shortened collagen fibers, and elevated expression of cartilage extracellular matrix genes, suggesting that perlecan protects cartilage extracellular matrix from degradation.

View Article: PubMed Central - PubMed

Affiliation: Department of Experimental Pathology, Lund University, S-221 85 Lund, Sweden.

ABSTRACT
Perlecan is a heparan sulfate proteoglycan that is expressed in all basement membranes (BMs), in cartilage, and several other mesenchymal tissues during development. Perlecan binds growth factors and interacts with various extracellular matrix proteins and cell adhesion molecules. Homozygous mice with a mutation in the perlecan gene exhibit normal formation of BMs. However, BMs deteriorate in regions with increased mechanical stress such as the contracting myocardium and the expanding brain vesicles showing that perlecan is crucial for maintaining BM integrity. As a consequence, small clefts are formed in the cardiac muscle leading to blood leakage into the pericardial cavity and an arrest of heart function. The defects in the BM separating the brain from the adjacent mesenchyme caused invasion of brain tissue into the overlaying ectoderm leading to abnormal expansion of neuroepithelium, neuronal ectopias, and exencephaly. Finally, homozygotes developed a severe defect in cartilage, a tissue that lacks BMs. The chondrodysplasia is characterized by a reduction of the fibrillar collagen network, shortened collagen fibers, and elevated expression of cartilage extracellular matrix genes, suggesting that perlecan protects cartilage extracellular matrix from degradation.

Show MeSH
Related in: MedlinePlus