Aspects of BMP-2 binding to receptors and collagen: Influence of cell senescence on receptor binding and absence of high-affinity stoichiometric binding to collagen

M. Laub, M. Chatzinikolaidou, H. P. Jennissen

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)


On the basis of their osteoinductive properties bone morphogenetic proteins (BMPs) are used today in clinical therapy such as the treatment of spinal disorders or healing defects in tibia fractures. A major biochemical function of these molecules is their binding to a large number of other proteins to fulfil their biological role. Two of these BMP-binding proteins are the cellular BMP-receptor and the collagen molecule which has been implicated as a specific BMP binding protein from the beginning of BMP-2 research. These two molecules are the subject of this paper. In receptor binding one must distinguish between the binding function (θ) and the state function (r). The binding function describes the equilibrium between effector (e.g. BMP-2) and the receptor, whereas the state function describes the change in receptor activation elicted by the effector resulting in downstream effects such as the induction of alkaline phosphatase. In studies on the state function of rhBMP-2 binding to MC3T3-E1 cells it will be shown that the binding affinity of the receptor decreases fivefold in a highly significant manner (p <0.0002, n = 10, duplicate assays) with the serial passage number from 1.7 ±0.3 nM as measured with passage 5 cells to 8.9 ±1.5 nM as measured with passage 10 cells. Since the serial passage model of MC3T3-E1 cells is a model of senescence it is concluded that the affinity of the rhBMP-2 receptor interaction decreases with senescence i.e. age. This may have important consequences for the age dependent dosage of rhBMP-2 in the clinic. In a second series of experiments it will be shown that contrary to widespread belief, BMP-2 does not show a high affinity stoichiometric binding to collagen as measured by affinity chromatography on collagen Sepharose and in solution by gel filtration. A review of the literature and evaluation of binding stoichiometry, interestingly supported our finding since the calculated stoichiomerties indicate a binding of 10-3 to 10-4 mol BMP/mol tropocollagen. It is suggested that collagen is substituted by porous calcium phosphates and metals as carriers for BMP applications.

Original languageEnglish
Pages (from-to)1019-1026
Number of pages8
JournalMaterialwissenschaft und Werkstofftechnik
Issue number12
Publication statusPublished - Dec 2007
Externally publishedYes


  • Anthelix
  • Anti-helix
  • BMP-2
  • Collagen
  • Molecular evolution
  • TGF-β

ASJC Scopus subject areas

  • Materials Science(all)
  • Condensed Matter Physics
  • Mechanics of Materials
  • Mechanical Engineering

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