Unraveling the human bone microenvironment beyond the classical extracellular matrix proteins: a human bone protein library

J Proteome Res. 2011 Oct 7;10(10):4725-33. doi: 10.1021/pr200522n. Epub 2011 Sep 21.


A characteristic feature of bone, differentiating it from other connective tissues, is the mineralized extracellular matrix (ECM). Mineral accounts for the majority of the bone tissue volume, being the remainder organic material mostly derived from collagen. This, and the fact that only a limited number of noncollagenous ECM proteins are described, provides a limited view of the bone tissue composition and bone metabolism, the more so considering the increasing understanding of ECM significance for cellular form and function. For this reason, we set out to analyze and extensively characterize the human bone proteome using large-scale mass spectrometry-based methods. Bone samples of four individuals were analyzed identifying 3038 unique proteins. A total of 1213 of these were present in at least 3 out of 4 bone samples. For quantification purposes, we were limited to noncollagenous proteins (NCPs) and we could quantify 1051 NCPs. Most classical bone matrix proteins mentioned in literature were detected but were not among the highly abundant ones. Gene ontology analyses identified high-abundance groups of proteins with a functional link to mineralization and mineral metabolism such as transporters, pyrophosphatase activity, and Ca(2+)-dependent phospholipid binding proteins. ECM proteins were as well overrepresented together with nucleosome and antioxidant activity proteins, which have not been extensively characterized as being important for bone. In conclusion, our data clearly demonstrates that human bone tissue is a reservoir of a wide variety of proteins. In addition to the classical osteoblast-derived ECM, we have identified many proteins from different sources and of unknown function in bone. Thus, this study represents an informative library of bone proteins forming a source for novel bone formation modulators as well as biomarkers for bone diseases such as osteoporosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Bone and Bones / metabolism*
  • Calcium / metabolism
  • Chromatography, Liquid / methods
  • Computational Biology / methods
  • Electrophoresis, Polyacrylamide Gel
  • Extracellular Matrix Proteins / metabolism*
  • Female
  • Humans
  • Male
  • Mass Spectrometry / methods
  • Middle Aged
  • Osteoarthritis / metabolism
  • Proteome
  • Tandem Mass Spectrometry / methods


  • Extracellular Matrix Proteins
  • Proteome
  • Calcium