Disease relevance of FMOD

• Fibromodulin (FMOD) was shown to be highly overexpressed in chronic lymphocytic leukemia (CLL) cells compared with normal B lymphocytes by gene expression profiling [1].
• By using western blotting and immunohistochemistry immunoreactive FMOD was detected in leiomyoma and myometrial tissue-extract and in LSMC and MSMC, connective tissue fibroblasts and arterial walls [2].
• Doubly deficient BGN/FMOD mice develop premature TMJ osteoarthritis (OA) [3].
• In this study, fibromodulin was expressed at the gene level (reverse transcription-polymerase chain reaction [RT-PCR]) in all patients with B-CLL (n = 75) and in most (5 of 7) patients with mantle cell lymphoma (MCL) [4].
• In human gingival tissues, staining of fibromodulin was detected in the connective tissue of inflamed gingiva associated with both gingivitis and periodontitis; whereas, weak staining for this molecule was noted in healthy gingival tissues [5].

High impact information on FMOD

• The number of T cells during 4 weeks of in vitro culture increased 2- to 3.5-fold and the number of T cells recognizing FMOD peptides bound to HLA-A2 dimers increased 10-fold [1].
• T cells not only recognized HLA-A2-binding FMOD peptides presented by transporter-associated with antigen-processing (TAP)-deficient T2 cells, but also FMOD overexpressing autologous CLL cells in an HLA-A2-restricted manner [1].
• Fibromodulin, an extracellular matrix protein: characterization of its unique gene and protein expression in B-cell chronic lymphocytic leukemia and mantle cell lymphoma [4].
• Fibromodulin as a novel tumor-associated antigen (TAA) in chronic lymphocytic leukemia (CLL), which allows expansion of specific CD8+ autologous T lymphocytes [1].
• Normal blood mononuclear cells (T and B lymphocytes, monocytes), tonsil B cells, and granulocytes did not express fibromodulin [4].

Biological context of FMOD

• Localization of the human fibromodulin gene (FMOD) to chromosome 1q32 and completion of the cDNA sequence [6].
• The results indicated that FMOD is expressed at significantly higher levels in leiomyoma as compared to myometrium from proliferative phase (two- to three-folds; P < 0.05), but not the secretory phase of the menstrual cycle, whereas GnRHa therapy reduced FMOD expression to levels detected in myometrium from proliferative phase (P = 0.05) [2].
• Structure and deduced amino acid sequence of the human fibromodulin gene [7].
• Addition of 50 microg/ml purified FM to the reconstituted articular surfaces inhibited cell adhesion by 71.2 +/- 13.9% (P < 0.0001) [8].
• In addition fibromodulin showed an upregulation in inflamed gingival tissue [5].

Anatomical context of FMOD

• In CLL samples derived from 16 different patients, high expression of FMOD by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) was detectable in contrast to normal B lymphocytes [1].
• In summary, FMOD was shown for the first time to be naturally processed and presented as TAA in primary CLL cells, enabling the expansion of autologous tumor-specific T cells [1].
• Microarray gene expression profiling revealed fibromodulin (FMOD) is among differentially expressed genes in leiomyoma (L) and myometrium [2].
• Biglycan was expressed by glomerular endothelial cells and, together with fibromodulin, was synthesized and deposited in distal tubular cells and collecting ducts [9].
• Differentiation was rapidly induced in cells cultured in the presence of TGF-beta 3 or -beta 2 and was accompanied by the early expression of fibromodulin and cartilage oligomeric matrix protein [10].

Associations of FMOD with chemical compounds

• This can be explained by the fact that fibromodulin also binds complement inhibitor factor H. Factor H and C1q bind to non-overlapping sites on fibromodulin, but none of the interactions is mediated by the negatively charged keratan sulfate substituents of fibromodulin [11].
• Further studies revealed that fibromodulin binds directly to the globular heads of C1q, leading to activation of C1 [11].
• The deduced amino acid sequence from the cDNA analysis indicates the presence of consensus leucine-rich repeats which are present in other small proteoglycans, decorin, biglycan, and fibromodulin [12].
• Small PGs (biglycan, decorin, and fibromodulin) in the same extracts were analyzed in 12% polyacrylamide gels [13].
• MGP binds to vitronectin but not collagen, fibromodulin, heparin, osteocalcin, chondroitin sulfate, laminin, ovalbumin or albumin [14].
• The collagen-binding Glu-353 and Lys-355 residues in fibromodulin are exposed on the exterior of the beta-sheet-loop structure of the leucine-rich repeat, which resembles the location of interacting residues in other leucine-rich repeat proteins, e.g. decorin [15].

Other interactions of FMOD

• In a time- and cell-dependent manner, TGF-beta1 (2.5 ng/ml) increased the expression of FMOD in MSMC, whereas GnRHa (0.1 microM) inhibited that in MSMC and LSMC (P < 0.05) [2].
• Interaction of the small interstitial proteoglycans biglycan, decorin and fibromodulin with transforming growth factor beta [16].
• Amplification by RT-PCR was required to detect the signals for fibromodulin and lumican [9].
• One granulation-tissue fibroblast strain that was composed exclusively of alpha-smooth-muscle actin-positive cells (myofibroblasts) expressed strongly elevated basal levels of biglycan, fibromodulin, and versican (the large chondroitin sulphate proteoglycan), as well as type I and III procollagen mRNA [17].
• The gene expression of matrix-associated proteoglycans (biglycan and fibromodulin) was also increased by FGF2 and hypoxia [18].

Analytical, diagnostic and therapeutic context of FMOD

• Circular dichroism spectra and fibrillogenesis inhibition studies show that fibromodulin structure and its collagen fibrillogenesis control function are strictly dependent on the presence of intact disulphide bridge(s) [19].
• The long-term cell culture revealed a late activation of the Col3alpha1, Col4alpha1 and Col11alpha1 genes as well as biglycan, fibromodulin and lumican [20].
• We, therefore, investigated the temporo-spatial expression of fibromodulin in vivo during endochondral bone formation by in situ hybridization [21].
• Peptide mapping of trappin-2 binding partners showed that fibromodulin was bound to trappin-2 in cartilage [22].
• METHODS: Lumbar intervertebral discs were obtained from individuals of different ages, and extracts of anulus fibrosus and nucleus pulposus were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting using antibodies specific for fibromodulin and lumican [23].

References