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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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ECM expression in long bones. (A and B) Safranin orange (SO) and van Kossa (vK) double staining show reduced proteoglycan content in mutant (B) as compared with wild-type (A) cartilage and the absence of mineralization of longitudinal septa in the lower hypertrophic zone (1 h) of the mutant growth plate (A and B). Also, note the transversally oriented trabecular bones in the mutant (arrows). (C–H) Immunostaining of perlecan and collagen types II (Col2) and X (Col10) on consecutive sections of elbows from normal and perlecan- E15.5 embryos. Perlecan is present in normal cartilage, in the periosteum/perichondrium, and in the surrounding connective tissues (C). In mutant embryos, perlecan staining is absent (D). The distribution of collagen types II (E and F) and X (G and H) is similar in normal (E and G) and perlecan- (F and H) cartilage. Bar: (A–D and G and H) 100 μm; 50 μm in E and F.
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Figure 7: ECM expression in long bones. (A and B) Safranin orange (SO) and van Kossa (vK) double staining show reduced proteoglycan content in mutant (B) as compared with wild-type (A) cartilage and the absence of mineralization of longitudinal septa in the lower hypertrophic zone (1 h) of the mutant growth plate (A and B). Also, note the transversally oriented trabecular bones in the mutant (arrows). (C–H) Immunostaining of perlecan and collagen types II (Col2) and X (Col10) on consecutive sections of elbows from normal and perlecan- E15.5 embryos. Perlecan is present in normal cartilage, in the periosteum/perichondrium, and in the surrounding connective tissues (C). In mutant embryos, perlecan staining is absent (D). The distribution of collagen types II (E and F) and X (G and H) is similar in normal (E and G) and perlecan- (F and H) cartilage. Bar: (A–D and G and H) 100 μm; 50 μm in E and F.

Mentions: Safranin-O staining was reduced in perlecan- cartilage, suggesting a decreased proteoglycan content (Fig. 7A and Fig. B). van Kossa staining revealed that normal bones showed clear mineralization in the longitudinal septa of the late hypertrophic zone (Fig. 7 A), perlecan- tissue had minimal or no mineral deposits in the matrix around hypertrophic chondrocytes, and the calcified trabecula were transversely oriented in perlecan- bones (Fig. 7 B). Immunohistochemistry showed expression of perlecan in cartilage as well as the surrounding mesenchyme of normal but not mutant mice (Fig. 7C and Fig. D). Matrix proteins including collagen types II, IX, X, and XI, aggrecan, matrilin-1 and -3, and COMP were expressed in homozygotes (Fig. 7F and Fig. H, and not shown).


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)

ECM expression in long bones. (A and B) Safranin orange (SO) and van Kossa (vK) double staining show reduced proteoglycan content in mutant (B) as compared with wild-type (A) cartilage and the absence of mineralization of longitudinal septa in the lower hypertrophic zone (1 h) of the mutant growth plate (A and B). Also, note the transversally oriented trabecular bones in the mutant (arrows). (C–H) Immunostaining of perlecan and collagen types II (Col2) and X (Col10) on consecutive sections of elbows from normal and perlecan- E15.5 embryos. Perlecan is present in normal cartilage, in the periosteum/perichondrium, and in the surrounding connective tissues (C). In mutant embryos, perlecan staining is absent (D). The distribution of collagen types II (E and F) and X (G and H) is similar in normal (E and G) and perlecan- (F and H) cartilage. Bar: (A–D and G and H) 100 μm; 50 μm in E and F.
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Figure 7: ECM expression in long bones. (A and B) Safranin orange (SO) and van Kossa (vK) double staining show reduced proteoglycan content in mutant (B) as compared with wild-type (A) cartilage and the absence of mineralization of longitudinal septa in the lower hypertrophic zone (1 h) of the mutant growth plate (A and B). Also, note the transversally oriented trabecular bones in the mutant (arrows). (C–H) Immunostaining of perlecan and collagen types II (Col2) and X (Col10) on consecutive sections of elbows from normal and perlecan- E15.5 embryos. Perlecan is present in normal cartilage, in the periosteum/perichondrium, and in the surrounding connective tissues (C). In mutant embryos, perlecan staining is absent (D). The distribution of collagen types II (E and F) and X (G and H) is similar in normal (E and G) and perlecan- (F and H) cartilage. Bar: (A–D and G and H) 100 μm; 50 μm in E and F.
Mentions: Safranin-O staining was reduced in perlecan- cartilage, suggesting a decreased proteoglycan content (Fig. 7A and Fig. B). van Kossa staining revealed that normal bones showed clear mineralization in the longitudinal septa of the late hypertrophic zone (Fig. 7 A), perlecan- tissue had minimal or no mineral deposits in the matrix around hypertrophic chondrocytes, and the calcified trabecula were transversely oriented in perlecan- bones (Fig. 7 B). Immunohistochemistry showed expression of perlecan in cartilage as well as the surrounding mesenchyme of normal but not mutant mice (Fig. 7C and Fig. D). Matrix proteins including collagen types II, IX, X, and XI, aggrecan, matrilin-1 and -3, and COMP were expressed in homozygotes (Fig. 7F and Fig. H, and not shown).

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