Unique cartilage matrix-associated protein regulates fibrillin-2 expression and directly interacts with fibrillin-2 protein independent of calcium binding

Biochem Biophys Res Commun. 2019 Apr 2;511(2):221-227. doi: 10.1016/j.bbrc.2019.01.128. Epub 2019 Feb 18.

Abstract

Unique cartilage matrix-associated protein (UCMA) is a secretory γ-carboxyglutamate (Gla) containing protein that is mainly expressed in the cartilage. Ucma, a downstream gene of both Runx2 and Osterix, has recently been described to promote osteoblast differentiation and matrix mineralization. However, till date, no studies have focused on the role of downstream target genes of Ucma in osteogenesis. Here, by Affymetrix GeneChip microarray analysis, we determined 45 differentially expressed genes in response to Ucma stable overexpression or knockdown in osteoblast cells, which provided insight into molecular mechanisms underlying osteoblast differentiation. In particular, we showed that fibrillin-2 (FBN2) expression was proportional to Ucma expression in osteoblasts as validated by quantitative PCR. We also showed that even though Gla-containing UCMA and calcium-binding EGF-like domain-containing FBN2 are known to have a high affinity for calcium, FBN2 whose expression was regulated by UCMA directly interacted with the UCMA protein, independent of calcium.

Keywords: Calcium; Fibrillin-2; Gene profile; Interaction; Microarray; Ucma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Cell Line
  • Extracellular Matrix Proteins / genetics
  • Extracellular Matrix Proteins / metabolism*
  • Fibrillin-2 / genetics
  • Fibrillin-2 / metabolism*
  • Gene Expression Regulation
  • Intracellular Signaling Peptides and Proteins
  • Mice
  • Osteoblasts / cytology
  • Osteoblasts / metabolism*
  • Osteogenesis
  • Protein Interaction Maps

Substances

  • Extracellular Matrix Proteins
  • Fibrillin-2
  • Intracellular Signaling Peptides and Proteins
  • Ucma protein, mouse
  • Calcium