Disease relevance of Bgn

• Accelerated osteoarthritis in the temporomandibular joint of biglycan/fibromodulin double-deficient mice [1].
• Age-related osteoporosis in biglycan-deficient mice is related to defects in bone marrow stromal cells [2].
• Bgn-deficient mice develop age-related osteopenia with a phenotype that resembles osteoporosis [3].
• Biglycan-null mice have a considerable survival benefit in LPS- or zymosan-induced sepsis due to lower levels of circulating TNF-alpha and reduced infiltration of mononuclear cells in the lung, which cause less end-organ damage [4].
• Biglycan is overexpressed in pancreatic cancer and induces G1-arrest in pancreatic cancer cell lines [5].

Psychiatry related information on Bgn

• These results provide the first experimental evidence that the atherogenic risk factor biglycan alters APP splicing and may participate in the pathogenesis of both Alzheimer and vascular dementias [6].

High impact information on Bgn

• In vitro studies indicate that Bgn may function in connective tissue metabolism by binding to collagen fibrils and TGF-beta (refs 5,6), and may promote neuronal survival [7].
• Although apparently normal at birth, these mice display a phenotype characterized by a reduced growth rate and decreased bone mass due to the absence of Bgn [7].
• Biglycan (encoded by the gene Bgn) is an ECM proteoglycan that is enriched in bone and other non-skeletal connective tissues [7].
• Similar repeats have been found in two other proteoglycans, biglycan and fibromodulin, and in several other proteins including Drosophila morphogenetic proteins [8].
• Thus, biglycan, upon release from the ECM or from macrophages, can boost inflammation by signaling through TLR4 and TLR2, thereby enhancing the synthesis of TNF-alpha and MIP-2 [4].

Chemical compound and disease context of Bgn

• There is growing evidence that the two small leucine-rich proteoglycans biglycan and decorin regulate the assembly of connective tissues and alter cell behavior during development and pathological processes [9].
• Prostacyclin (PGI) receptor binding and cyclic AMP synthesis activities of PGI1 analogues, SM-10906 and its methyl ester, SM-10902, in mastocytoma P-815 cells [10].

Biological context of Bgn

• The mouse Bgn gene spanned over 9.5 kb of continuous DNA and comprised 8 exons, with a perfectly conserved intron/exon organization vis-á-vis the human counterpart [11].
• A transient and dramatic up-regulation of biglycan was associated with newly formed myotubes, whereas decorin presented only minor variations [12].
• We have cloned and sequenced the cDNA containing the complete murine biglycan, elucidated its genomic organization, and demonstrated functional promoter activity of its 5' flanking region [11].
• The data suggest that differences in tissue distribution are responsible for the different effects on TGF-beta bioactivity in vivo, indicating that decorin, but not biglycan, has potential therapeutic value in fibrotic disorders of the lung [13].
• Biglycan is a Class I Small Leucine Rich Proteoglycans (SLRP) that is localized on human chromosome Xq28-ter [14].

Anatomical context of Bgn

• Phenotypic effects of biglycan deficiency are linked to collagen fibril abnormalities, are synergized by decorin deficiency, and mimic Ehlers-Danlos-like changes in bone and other connective tissues [15].
• Studies both in vitro and in intact developing newborn mice showed that biglycan expression is initially high and then decreases during skeletal muscle differentiation and maturation [12].
• Biglycan mRNA was ubiquitously distributed throughout the palatal mesenchyme for the mid-gestation period [16].
• OBJECTIVE: To investigate whether the absence of biglycan and fibromodulin, two proteoglycans expressed in cartilage, bone and tendon, resulted in accelerated osteoarthritis in the temporomandibular joint (TMJ) [1].
• METHODS: Histological sections of TMJ from 3-, 6-, 9- and 18-month-old wild-type (WT) and biglycan/fibromodulin double-deficient (DKO) mice were compared [1].

Associations of Bgn with chemical compounds

• Here, we show that BMP-1 cleaves probiglycan at a single site, removing the propeptide and producing a biglycan molecule with an NH(2) terminus identical to that of the mature form found in tissues [17].
• We evaluated biglycan and decorin expression in skeletal muscle during barium chloride-induced skeletal muscle regeneration in mice [12].
• Biglycan, a member of the small leucine-rich protein family, was suspected of contributing to this process [6].
• On the other hand, biglycan in the retinoic acid-treated mice did not show remarkable change in its distribution patterns compared with that in the control mice [16].
• The biglycan glycosaminoglycan chains were found to contain a similar ratio of 4-sulphate/6-sulphate, but with approx. 40-45% of the glucuronic acid epimerized to iduronic acid [18].

Physical interactions of Bgn

• In addition, in vitro analysis revealed that biglycan binds to TGF-alpha, thus interrupting EGFR signaling pathways essential for mesenchymal cell migration induced by eyelid epithelium [19].
• Biglycan (bgn) is a small proteoglycan in skeletal tissue that binds and regulates collagen and TGF-beta activities [20].

Regulatory relationships of Bgn

• APP mRNA splicing is upregulated in the brain of biglycan transgenic mice [6].
• The results from gene expression profiling reveal the ability of mimecan to influence expression of biglycan and chondroadherin, thereby indicating possible novel regulatory interactions between these SLRP family members [21].
• By signaling through TLR2/4, biglycan stimulates the expression of NLRP3 and pro-IL-1beta mRNA [22].

Other interactions of Bgn

• The constitutive expression of syndecan-4, glypican-1 and biglycan in glomerular cells points to a role for these polyanionic molecules in maintaining the integrity of the glomerular filtration barrier [23].
• Biglycan (bgn) is an extracellular matrix proteoglycan that is enriched in bone and other skeletal connective tissues [2].
• RT-PCR revealed that both factors upregulated mRNA of aggrecan more than that of biglycan and decorin [24].
• Abnormal collagen fibrils in tendons of biglycan/fibromodulin-deficient mice lead to gait impairment, ectopic ossification, and osteoarthritis [25].
• In contrast, in biglycan-deficient kidneys the overexpression of fibrillin-1 was markedly attenuated and this was associated with cystic dilatation of Bowman's capsule and proximal tubules [9].

Analytical, diagnostic and therapeutic context of Bgn

• The individual and combined overexpressions of biglycan and apoB-100 were therefore examined on the cortical APP mRNA levels of transgenic mice by means of semiquantitative PCR [6].
• Adenoviral gene transfer was used to overexpress active TGF-beta, decorin, and biglycan in cell culture and in murine lungs [13].
• CONCLUSION: The biglycan/fibromodulin double knock-out mouse constitutes a useful animal model to decipher the pathobiology of osteoarthritis in the TMJ [1].
• Transmission electron microscopy analysis showed that like the decorin and biglycan knockouts, they have severely disturbed collagen fibril structures [14].
• In situ hybridization studies for periostin [osteoblast-specific factor 2 (fasciclin I-like)] and biglycan revealed that these genes are restricted to mesenchymal derivatives during embryogenesis and are significantly regulated during regeneration of the injured hindlimb skeletal muscle [26].

References