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Differential expression of lumican and fibromodulin regulate collagen fibrillogenesis in developing mouse tendons.

Ezura Y, Chakravarti S, Oldberg A, Chervoneva I, Birk DE - J. Cell Biol. (2000)

Bottom Line: With development, the amount of lumican decreases to barely detectable levels while fibromodulin increases significantly, and these changing patterns may regulate this process.The observed increased ratio of fibromodulin to lumican and a competition for the same binding site could mediate these transitions.These studies indicate that lumican and fibromodulin have different developmental stage and leucine-rich repeat protein specific functions in the regulation of fibrillogenesis.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.

ABSTRACT
Collagen fibrillogenesis is finely regulated during development of tissue-specific extracellular matrices. The role(s) of a leucine-rich repeat protein subfamily in the regulation of fibrillogenesis during tendon development were defined. Lumican-, fibromodulin-, and double-deficient mice demonstrated disruptions in fibrillogenesis. With development, the amount of lumican decreases to barely detectable levels while fibromodulin increases significantly, and these changing patterns may regulate this process. Electron microscopic analysis demonstrated structural abnormalities in the fibrils and alterations in the progression through different assembly steps. In lumican-deficient tendons, alterations were observed early and the mature tendon was nearly normal. Fibromodulin-deficient tendons were comparable with the lumican- in early developmental periods and acquired a severe phenotype by maturation. The double-deficient mice had a phenotype that was additive early and comparable with the fibromodulin-deficient mice at maturation. Therefore, lumican and fibromodulin both influence initial assembly of intermediates and the entry into fibril growth, while fibromodulin facilitates the progression through growth steps leading to mature fibrils. The observed increased ratio of fibromodulin to lumican and a competition for the same binding site could mediate these transitions. These studies indicate that lumican and fibromodulin have different developmental stage and leucine-rich repeat protein specific functions in the regulation of fibrillogenesis.

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Related in: MedlinePlus

Collagen fibril structure during development in normal wild-type, lumican-, fibromodulin-, and double lumican/fibromodulin–deficient mice. Transmission electron micrographs of transverse sections from mouse flexor tendons from normal mice (a–d) and mutant mice (e–p). Fibril structure was analyzed at different developmental stages between 4 d and 3 mo postnatal, 4 d (a, e, i, and m), 10 d (b, f, j, and n), 1 mo (c, g, k, and o), and 3 mo (d, h, l, and p) postnatal. Arrows indicate fibrils with diameters of ∼64 nm, the diameter seen in normal 4-d postnatal tendons. Arrowheads indicate irregular fibril profiles. Bar, 300 nm.
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Figure 5: Collagen fibril structure during development in normal wild-type, lumican-, fibromodulin-, and double lumican/fibromodulin–deficient mice. Transmission electron micrographs of transverse sections from mouse flexor tendons from normal mice (a–d) and mutant mice (e–p). Fibril structure was analyzed at different developmental stages between 4 d and 3 mo postnatal, 4 d (a, e, i, and m), 10 d (b, f, j, and n), 1 mo (c, g, k, and o), and 3 mo (d, h, l, and p) postnatal. Arrows indicate fibrils with diameters of ∼64 nm, the diameter seen in normal 4-d postnatal tendons. Arrowheads indicate irregular fibril profiles. Bar, 300 nm.

Mentions: The formation of collagen fibrils during tendon development in mice deficient in lumican, fibromodulin, or both was analyzed. The fibrils from lumican-, fibromodulin-, and double lumican/fibromodulin–deficient mice showed abnormalities during development relative to the wild-type controls (Fig. 5). Structurally, three distinct abnormalities were observed. First was the premature presence of fibril diameter heterogeneity in the 4-d double-deficient tendon relative to the wild-type controls (Fig. 5, a and m). Secondly, there was an abnormally large number of small diameter fibrils present in the later stages of development, best seen at 3 mo, in the fibromodulin- and double-deficient mice (Fig. 5l and Fig. p). Finally, all three deficient conditions had fibrils with irregular profiles, indicative of abnormal lateral association or a defect in molecular rearrangement after fusion. The 1–3-mo fibromodulin- and double-deficient tendons had large numbers of very abnormal “cauliflower” fibrils, with the double-deficient tendons showing the most severe phenotype (Fig. 5k, Fig. l, Fig. o, and Fig. p). In contrast, the lumican-deficient tendons contained fibrils only slightly irregular in profile at 1–3 mo (Fig. 5g and Fig. h).


Differential expression of lumican and fibromodulin regulate collagen fibrillogenesis in developing mouse tendons.

Ezura Y, Chakravarti S, Oldberg A, Chervoneva I, Birk DE - J. Cell Biol. (2000)

Collagen fibril structure during development in normal wild-type, lumican-, fibromodulin-, and double lumican/fibromodulin–deficient mice. Transmission electron micrographs of transverse sections from mouse flexor tendons from normal mice (a–d) and mutant mice (e–p). Fibril structure was analyzed at different developmental stages between 4 d and 3 mo postnatal, 4 d (a, e, i, and m), 10 d (b, f, j, and n), 1 mo (c, g, k, and o), and 3 mo (d, h, l, and p) postnatal. Arrows indicate fibrils with diameters of ∼64 nm, the diameter seen in normal 4-d postnatal tendons. Arrowheads indicate irregular fibril profiles. Bar, 300 nm.
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2169450&req=5

Figure 5: Collagen fibril structure during development in normal wild-type, lumican-, fibromodulin-, and double lumican/fibromodulin–deficient mice. Transmission electron micrographs of transverse sections from mouse flexor tendons from normal mice (a–d) and mutant mice (e–p). Fibril structure was analyzed at different developmental stages between 4 d and 3 mo postnatal, 4 d (a, e, i, and m), 10 d (b, f, j, and n), 1 mo (c, g, k, and o), and 3 mo (d, h, l, and p) postnatal. Arrows indicate fibrils with diameters of ∼64 nm, the diameter seen in normal 4-d postnatal tendons. Arrowheads indicate irregular fibril profiles. Bar, 300 nm.
Mentions: The formation of collagen fibrils during tendon development in mice deficient in lumican, fibromodulin, or both was analyzed. The fibrils from lumican-, fibromodulin-, and double lumican/fibromodulin–deficient mice showed abnormalities during development relative to the wild-type controls (Fig. 5). Structurally, three distinct abnormalities were observed. First was the premature presence of fibril diameter heterogeneity in the 4-d double-deficient tendon relative to the wild-type controls (Fig. 5, a and m). Secondly, there was an abnormally large number of small diameter fibrils present in the later stages of development, best seen at 3 mo, in the fibromodulin- and double-deficient mice (Fig. 5l and Fig. p). Finally, all three deficient conditions had fibrils with irregular profiles, indicative of abnormal lateral association or a defect in molecular rearrangement after fusion. The 1–3-mo fibromodulin- and double-deficient tendons had large numbers of very abnormal “cauliflower” fibrils, with the double-deficient tendons showing the most severe phenotype (Fig. 5k, Fig. l, Fig. o, and Fig. p). In contrast, the lumican-deficient tendons contained fibrils only slightly irregular in profile at 1–3 mo (Fig. 5g and Fig. h).

Bottom Line: With development, the amount of lumican decreases to barely detectable levels while fibromodulin increases significantly, and these changing patterns may regulate this process.The observed increased ratio of fibromodulin to lumican and a competition for the same binding site could mediate these transitions.These studies indicate that lumican and fibromodulin have different developmental stage and leucine-rich repeat protein specific functions in the regulation of fibrillogenesis.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.

ABSTRACT
Collagen fibrillogenesis is finely regulated during development of tissue-specific extracellular matrices. The role(s) of a leucine-rich repeat protein subfamily in the regulation of fibrillogenesis during tendon development were defined. Lumican-, fibromodulin-, and double-deficient mice demonstrated disruptions in fibrillogenesis. With development, the amount of lumican decreases to barely detectable levels while fibromodulin increases significantly, and these changing patterns may regulate this process. Electron microscopic analysis demonstrated structural abnormalities in the fibrils and alterations in the progression through different assembly steps. In lumican-deficient tendons, alterations were observed early and the mature tendon was nearly normal. Fibromodulin-deficient tendons were comparable with the lumican- in early developmental periods and acquired a severe phenotype by maturation. The double-deficient mice had a phenotype that was additive early and comparable with the fibromodulin-deficient mice at maturation. Therefore, lumican and fibromodulin both influence initial assembly of intermediates and the entry into fibril growth, while fibromodulin facilitates the progression through growth steps leading to mature fibrils. The observed increased ratio of fibromodulin to lumican and a competition for the same binding site could mediate these transitions. These studies indicate that lumican and fibromodulin have different developmental stage and leucine-rich repeat protein specific functions in the regulation of fibrillogenesis.

Show MeSH
Related in: MedlinePlus