Original Article

Differential Expression of Lumican and Fibromodulin Regulate Collagen Fibrillogenesis in Developing Mouse Tendons

Correspondence to: David E. Birk, Department of Pathology, Anatomy & Cell Biology, Jefferson Medical College, 1020 Locust Street, JAH543, Philadelphia, PA 19107. Tel:(215) 503-7855 Fax:(215) 923-9618

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-null 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.

Key Words: collagen, proteoglycans, lumican, fibromodulin, tendon

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Kalamajski, S., Oldberg, A. (2009). Homologous Sequence in Lumican and Fibromodulin Leucine-rich Repeat 5-7 Competes for Collagen Binding. J. Biol. Chem. 284: 534-539 [Abstract] [Full Text]  
• Wu, F., Chakravarti, S. (2007). Differential Expression of Inflammatory and Fibrogenic Genes and Their Regulation by NF-{kappa}B Inhibition in a Mouse Model of Chronic Colitis. J. Immunol. 179: 6988-7000 [Abstract] [Full Text]  
• Halasz, K., Kassner, A., Morgelin, M., Heinegard, D. (2007). COMP Acts as a Catalyst in Collagen Fibrillogenesis. J. Biol. Chem. 282: 31166-31173 [Abstract] [Full Text]  
• Kalamajski, S., Oldberg, A. (2007). Fibromodulin Binds Collagen Type I via Glu-353 and Lys-355 in Leucine-rich Repeat 11. J. Biol. Chem. 282: 26740-26745 [Abstract] [Full Text]  
• Wu, F., Vij, N., Roberts, L., Lopez-Briones, S., Joyce, S., Chakravarti, S. (2007). A Novel Role of the Lumican Core Protein in Bacterial Lipopolysaccharide-induced Innate Immune Response. J. Biol. Chem. 282: 26409-26417 [Abstract] [Full Text]  
• Rentz, T. J., Poobalarahi, F., Bornstein, P., Sage, E. H., Bradshaw, A. D. (2007). SPARC Regulates Processing of Procollagen I and Collagen Fibrillogenesis in Dermal Fibroblasts. J. Biol. Chem. 282: 22062-22071 [Abstract] [Full Text]  
• Murchison, N. D., Price, B. A., Conner, D. A., Keene, D. R., Olson, E. N., Tabin, C. J., Schweitzer, R. (2007). Regulation of tendon differentiation by scleraxis distinguishes force-transmitting tendons from muscle-anchoring tendons. Development 134: 2697-2708 [Abstract] [Full Text]  
• Goldberg, M., Septier, D., Oldberg, A., Young, M. F., Ameye, L. G. (2006). Fibromodulin-deficient Mice Display Impaired Collagen Fibrillogenesis in Predentin as Well as Altered Dentin Mineralization and Enamel Formation. J. Histochem. Cytochem. 54: 525-537 [Abstract] [Full Text]  
• Carlson, E. C., Liu, C.-Y., Chikama, T.-i., Hayashi, Y., Kao, C. W.-C., Birk, D. E., Funderburgh, J. L., Jester, J. V., Kao, W. W.-Y. (2005). Keratocan, a Cornea-specific Keratan Sulfate Proteoglycan, Is Regulated by Lumican. J. Biol. Chem. 280: 25541-25547 [Abstract] [Full Text]  
• Levens, E., Luo, X., Ding, L., Williams, R. S., Chegini, N. (2005). Fibromodulin is expressed in leiomyoma and myometrium and regulated by gonadotropin-releasing hormone analogue therapy and TGF-{beta} through Smad and MAPK-mediated signalling. Mol Hum Reprod 11: 489-494 [Abstract] [Full Text]  
• Amenta, P. S., Scivoletti, N. A., Newman, M. D., Sciancalepore, J. P., Li, D., Myers, J. C. (2005). Proteoglycan-Collagen XV in Human Tissues Is Seen Linking Banded Collagen Fibers Subjacent to the Basement Membrane. J. Histochem. Cytochem. 53: 165-176 [Abstract] [Full Text]  
• Docheva, D., Hunziker, E. B., Fassler, R., Brandau, O. (2005). Tenomodulin Is Necessary for Tenocyte Proliferation and Tendon Maturation. Mol. Cell. Biol. 25: 699-705 [Abstract] [Full Text]  
• Dunlevy, J. R., Rada, J. A. S. (2004). Interaction of Lumican with Aggrecan in the Aging Human Sclera. IOVS 45: 3849-3856 [Abstract] [Full Text]  
• Chen, Y., Lasaitiene, D., Gabrielsson, B. G., Carlsson, L. M.S., Billig, H., Carlsson, B., Marcussen, N., Sun, X.-F., Friberg, P. (2004). Neonatal Losartan Treatment Suppresses Renal Expression of Molecules Involved in Cell-Cell and Cell-Matrix Interactions. J. Am. Soc. Nephrol. 15: 1232-1243 [Abstract] [Full Text]  
• KJAeR, M. (2004). Role of Extracellular Matrix in Adaptation of Tendon and Skeletal Muscle to Mechanical Loading. Physiol. Rev. 84: 649-698 [Abstract] [Full Text]  
• Hansen, U., Bruckner, P. (2003). Macromolecular Specificity of Collagen Fibrillogenesis: FIBRILS OF COLLAGENS I AND XI CONTAIN A HETEROTYPIC ALLOYED CORE AND A COLLAGEN I SHEATH. J. Biol. Chem. 278: 37352-37359 [Abstract] [Full Text]  
• Porter, J. D., Merriam, A. P., Leahy, P., Gong, B., Khanna, S. (2003). Dissection of temporal gene expression signatures of affected and spared muscle groups in dystrophin-deficient (mdx) mice. Hum Mol Genet 12: 1813-1821 [Abstract] [Full Text]  
• Chakravarti, S., Paul, J., Roberts, L., Chervoneva, I., Oldberg, A., Birk, D. E. (2003). Ocular and Scleral Alterations in Gene-Targeted Lumican-Fibromodulin Double-Null Mice. IOVS 44: 2422-2432 [Abstract] [Full Text]  
• Berryhill, B. L., Kader, R., Kane, B., Birk, D. E., Feng, J., Hassell, J. R. (2002). Partial Restoration of the Keratocyte Phenotype to Bovine Keratocytes Made Fibroblastic by Serum. IOVS 43: 3416-3421 [Abstract] [Full Text]  
• Jepsen, K. J., Wu, F., Peragallo, J. H., Paul, J., Roberts, L., Ezura, Y., Oldberg, A., Birk, D. E., Chakravarti, S. (2002). A Syndrome of Joint Laxity and Impaired Tendon Integrity in Lumican- and Fibromodulin-deficient Mice. J. Biol. Chem. 277: 35532-35540 [Abstract] [Full Text]  
• Ameye, L., Young, M. F. (2002). Mice deficient in small leucine-rich proteoglycans: novel in vivo models for osteoporosis, osteoarthritis, Ehlers-Danlos syndrome, muscular dystrophy, and corneal diseases. Glycobiology 12: 107R-116R [Abstract] [Full Text]  
• Austin, B. A., Coulon, C., Liu, C.-Y., Kao, W. W.-Y., Rada, J. A. (2002). Altered Collagen Fibril Formation in the Sclera of Lumican-Deficient Mice. IOVS 43: 1695-1701 [Abstract] [Full Text]  
• AMEYE, L., ARIA, D., JEPSEN, K., OLDBERG, A., XU, T., YOUNG, M. F. (2002). Abnormal collagen fibrils in tendons of biglycan/fibromodulin-deficient mice lead to gait impairment, ectopic ossification, and osteoarthritis. FASEB J. 16: 673-680 [Abstract] [Full Text]  
• Schwartz, N. B., Domowicz, M. (2002). Chondrodysplasias due to proteoglycan defects. Glycobiology 12: 57R-68R [Abstract] [Full Text]  
• Levens, E., Luo, X., Ding, L., Williams, R. S., Chegini, N. (2005). Fibromodulin is expressed in leiomyoma and myometrium and regulated by gonadotropin-releasing hormone analogue therapy and TGF-{beta} through Smad and MAPK-mediated signalling. Mol Hum Reprod 11: 489-494 [Abstract] [Full Text]  
• Henry, S. P., Takanosu, M., Boyd, T. C., Mayne, P. M., Eberspaecher, H., Zhou, W., de Crombrugghe, B., Hook, M., Mayne, R. (2001). Expression Pattern and Gene Characterization of Asporin. A NEWLY DISCOVERED MEMBER OF THE LEUCINE-RICH REPEAT PROTEIN FAMILY. J. Biol. Chem. 276: 12212-12221 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents