Structure and biological function

Asporin is a 380 amino acid long, secreted dimeric extracellular matrix protein, which functions as a direct binding partner for TGFβ-1 and, like Decorin and Biglycan, belongs to the der Small Leucine- Rich Proteins (SLRP) class I family. They are characterised by a high degree of homology at the genetic and molecular level and the presence of leucine- rich repeats (LRRs), which are flanked by disulfides formed by cysteine residues. Unlike other members of the SLRP class II family, Asporin does not contain a glycosaminoglycan binding site, but it has several unique aspartic acid repeats in the N-Terminal region. The main biological function of Asporin most likely consists in the regulation of TGF-β1 activity to which it binds directly

Involvement in diseases:

Growing evidence demonstrates that Asporin is involved in the pathogenesis of osteoarthritis. Its expression is markedly increased in OA cartilage as compared with normal cartilage. Although the precise mechanism of OA induction by Asporin is not known yet, the inhibition of TGF-β1, a regulator of osteogenesis and chondrogenesis in articular cartilage and subchondral bone, my be the primary way of OA induction by Asporin
  • Asporin and Osteoarthritis
  • Xu et a., Osteoarthritis and Cartilage Volume 23, Issue 6, June 2015, Pages 933-939
  • Replication of association of the D-repeat polymorphism in asporin with osteoarthristis
  • Ikegawa et al., Arthritis Res Ther. 2006; 8(4): 403.
    t has been shown that Asporin expression in vertebral discs increases with age and degeneration The mechanisms of cartilage degeneration may be similar to those found in the pathogenesis of OA. Comparative analyses of asporin levels in OA and LDD or any other degenerative cartilage diseases may help in developing new therapeutic and preventative treatments.
  • Cartilage Intermediate Layer Protein and Asporin Polymorphisms Are Independent Risk Factors of Lumbar Disc Degeneration in Male Collegiate Athletes
  • Seok-Ki et al.,- Cartilage. 2014 Jan; 5(1): 37–42.
  • Asporin, a susceptibility gene in osteoarthritis, is expressed at higher levels in the more degenerate human intervertebral disc
  • Gruber et al., Arthritis Res Ther. 2009; 11(2): R47.
    TGF-β1 is well known to be secreted by cancer cells to modify their microenvironment and promoting invasive tumor growth. It has been demonstrated that high expression of Asporin is associated with less aggressive tumors and better prognosis. Thus, Asporin could be diagnostic and prognostic marker, having the potential to stratify cancer patients and identify those who are in need for more clinical attention.
  • The dual role of asporin in breast cancer progression.
  • Simkova et al., Oncotarget. 2016 Aug 9; 7(32): 52045–52060.
  • Asporin is a stromally expressed marker associated with prostate cancer progression
  • Rochette et al. Br J Cancer. 2017 Mar 14; 116(6): 775–784.
  • Asporin Is a Fibroblast-Derived TGF-β1 Inhibitor and a Tumor Suppressor Associated with Good Prognosis in Breast Cancer.
  • Maris et al., PLoS Med. 2015 Sep 1;12(9)