title: Biglycan fragmentation in pathologies associated with extracellular matrix remodeling by matrix metalloproteinases.
abstract: BACKGROUND
  The proteoglycan biglycan (BGN) is involved in collagen fibril assembly and its fragmentation is likely to be associated with collagen turnover during the pathogenesis of diseases which involve dysregulated extracellular matrix remodeling (ECMR), such as rheumatoid arthritis (RA) and liver fibrosis. The scope of the present study was to develop a novel enzyme-linked immunosorbent assay (ELISA) for the measurement of a MMP-9 and MMP-12-generated biglycan neo-epitope and to test its biological validity in a rat model of RA and in two rat models of liver fibrosis, chosen as models of ECMR.
  
  
  RESULTS
  Biglycan was cleaved in vitro by MMP-9 and -12 and the 344'YWEVQPATFR'353 peptide (BGM) was chosen as a potential neo-epitope. A technically sound competitive ELISA for the measurement of BGM was generated and the assay was validated in a bovine cartilage explant culture (BEX), in a collagen induced model of rheumatoid arthritis (CIA) and in two different rat models of liver fibrosis: the carbon tetrachloride (CCL4)-induced fibrosis model, and the bile duct ligation (BDL) model. Significant elevation in serum BGM was found in CIA rats compared to controls, in rats treated with CCL4 for 16 weeks and 20 weeks compared to the control groups as well as in all groups of rats subject to BDL compared with sham operated groups. Furthermore, there was a significant correlation of serum BGM levels with the extent of liver fibrosis determined by the Sirius red staining of liver sections in the CCL4 model.
  
  
  CONCLUSIONS
  We demonstrated that the specific tissue remodeling product of MMPs-degraded biglycan, namely the neo-epitope BGM, is correlated with pathological ECMR. This assay represents both a novel marker of ECM turnover and a potential new tool to elucidate biglycan role during the pathological processes associated with ECMR.
authors: Nordic Bioscience A/S, Herlev Hovedgade 207, Herlev, DK-2730, Denmark. fge@nordicbioscience.com.
authors: Federica
authors: F
authors: Genovese
authors: Natasha
authors: N
authors: Barascuk
authors: Lise
authors: L
authors: Larsen
authors: Martin Røssel
authors: MR
authors: Larsen
authors: Arkadiusz
authors: A
authors: Nawrocki
authors: Yili
authors: Y
authors: Li
authors: Qinlong
authors: Q
authors: Zheng
authors: Jianxia
authors: J
authors: Wang
authors: Sanne Skovgård
authors: SS
authors: Veidal
authors: Diana Julie
authors: DJ
authors: Leeming
authors: Morten Asser
authors: MA
authors: Karsdal
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