High impact information on FMOD

• A collagen-binding 59-kd protein (fibromodulin) is structurally related to the small interstitial proteoglycans PG-S1 and PG-S2 (decorin) [1].
• The cleavage product obtained after MMP-13 digestion was identical to that observed in cleaved fibromodulin from cartilage explant cultures stimulated with interleukin-1 [2].
• Cleavage removes the tyrosine sulfate-rich region in the N terminus of fibromodulin [2].
• Fibromodulin, a member of the leucine-rich repeat protein family, is one predominant protein in cartilage and is known for its roles in the formation of collagen fibrils and sustained interaction with these formed fibers [2].
• The deduced keratocan amino acid sequence is unique but related to two other keratan sulfate-containing proteins, lumican (the 37B core protein) and fibromodulin [3].

Biological context of FMOD

• Posttranslational modifications of fibromodulin [4].
• For fibromodulin, the data indicated an average of one binding site per collagen I molecule (Kd = 9.9 nM) [5].
• These findings are discussed in relation to the regulation of fibromodulin glycosylation and the likely influence of polylactosamine structure on the extracellular interactions and turnover of fibromodulin [6].
• These biochemical as well as immunohistochemical data suggest that the major KSPGs of cementum, lumican and fibromodulin, have a specific tissue distribution and may have regulatory roles in cementum mineralization [7].

Anatomical context of FMOD

• The small keratan sulfate-substituted proteoglycan (fibromodulin) from articular cartilage was shown to contain keratan sulfate linked to the core protein through N-glycosidic linkages to residues Asn-109, Asn-147, Asn-182, and Asn-272 [8].
• Biosynthetic experiments with articular chondrocytes in the presence of tunicamycin, an inhibitor of N-linked oligosaccharide synthesis, demonstrated a specific inhibition of [35S]SO4 incorporation into fibromodulin [8].
• Thus fibromodulin from cartilage, tendon, and sclera contains N-glycosidically linked oligosaccharides, some of which are extended to keratan sulfate chains [4].
• Among a large number of secreted fibroblast products, decorin and fibromodulin represented the vast majority of the collagen binding components [5].
• The small proteoglycans, decorin, fibromodulin, biglycan, and lumican, represent a family of structurally related but genetically distinct molecules present in many types of connective tissues [5].

Associations of FMOD with chemical compounds

• Cleavage of fibromodulin in cartilage explants involves removal of the N-terminal tyrosine sulfate-rich region by proteolysis at a site that is sensitive to matrix metalloproteinase-13 [2].
• These data demonstrate that there are fundamental differences between the structures present in the N-linked keratan sulphate chains attached to fibromodulin from articular cartilage and those from tracheal cartilage, which lack both alpha(2-6)-linked N-acetylneuraminic acid and alpha(1-3)-linked fucose [9].
• Biosynthetic mechanisms for the addition of polylactosamine to chondrocyte fibromodulin [6].
• Chondrocytes were treated with castanospermine, 1-(+)deoxymannojirimycin, and swainsonine, radiolabeled with [3,4,5-3H]leucine, [2-3H]mannose, or [6-3H]glucosamine, and newly synthesized fibromodulin was immunoprecipitated for analysis [6].
• It has been shown that in fibromodulin from young articular cartilage, the KS chains do not possess either non-reducing terminal (alpha2-6)-linked N-acetylneuraminic acid or fucose (alpha1-3)-linked to sulphated N-acetylglucosamine residues [10].

Other interactions of FMOD

• Bovine lumican had about 50% identity to bovine fibromodulin and 20% identity to bovine decorin and biglycan [11].
• The major extracted components were identified as decorin, Type VI collagen, fibromodulin and a member of the leucine rich repeat protein family (PRELP) [12].

Analytical, diagnostic and therapeutic context of FMOD

• Isolation of glycosylated peptides from tryptic digests of fibromodulin by ion-exchange chromatography and reversed-phase high performance liquid chromatography revealed four separate hexosamine-rich species, that were also immunoreactive with monoclonal antibody 5D4 [8].
• Fibromodulin substituted with keratan sulfate was purified from bovine articular cartilage extracts by density gradient centrifugation, ion-exchange chromatography, and gel-permeation chromatography [8].
• Digestion of fibromodulin with N-glycosidase F reduced the apparent size of fibromodulin to that of the core protein, as predicted from sequence analysis (Oldberg, A., Antonsson, P., Lindblom, K., and Heinegård, D. (1989) EMBO J.8, 2601-2604) [4].
• Immunoprecipitation of [3H]leucine-labeled decorin, aggrecan, and fibromodulin from cells showed that aggrecan and fibromodulin were not substituted with glycosamino-glycans, whereas all decorin molecules synthesized under these conditions were substituted with chondroitin [13].
• Fibromodulin appeared as a single polydisperse band with an apparent molecular weight (MW) of 80,000 (80 kDa) on SDS-PAGE [14].

References