Differential growth factor adsorption to calvarial osteoblast-secreted extracellular matrices instructs osteoblastic behavior

Archana Bhat, Simeon Boyd, Craig W Senders, Jonathan K Leach

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Craniosynostosis (CS), the premature ossification of cranial sutures, is attributed to increased osteogenic potential of resident osteoblasts, yet the contribution of the surrounding extracellular matrix (ECM) on osteogenic differentiation is unclear. The osteoblast-secreted ECM provides binding sites for cellular adhesion and regulates the transport and signaling of osteoinductive factors secreted by the underlying dura mater. The binding affinity of each osteoinductive factor for the ECM may amplify or mute its relative effect, thus contributing to the rate of suture fusion. The purpose of this paper was to examine the role of ECM composition derived from calvarial osteoblasts on protein binding and its resultant effect on cell phenotype. We hypothesized that potent osteoinductive proteins present during sutural fusion (e.g., bone morphogenetic protein-2 (BMP-2) and transforming growth factor beta-1 (TGF-β1)) would exhibit distinct differences in binding when exposed to ECMs generated by human calvarial osteoblasts from unaffected control individuals (CI) or CS patients. Decellularized ECMs produced by osteoblasts from CI or CS patients were incubated in the presence of BMP-2 or TGF-β1, and the affinity of each protein was analyzed. The contribution of ECM composition to protein binding was interrogated by enzymatically modulating proteoglycan content within the ECM. BMP-2 had a similar binding affinity for each ECM, while TGF-β1 had a greater affinity for ECMs produced by osteoblasts from CI compared to CS patients. Enzymatic treatment of ECMs reduced protein binding. CS osteoblasts cultured on enzymatically-treated ECMs secreted by osteoblasts from CI patients in the presence of BMP-2 exhibited impaired osteogenic differentiation compared to cells on untreated ECMs. These data demonstrate the importance of protein binding to cell-secreted ECMs and confirm that protein-ECM interactions have an important role in directing osteoblastic differentiation of calvarial osteoblasts.

Original languageEnglish (US)
Article numbere25990
JournalPLoS One
Volume6
Issue number10
DOIs
StatePublished - Oct 5 2011

Fingerprint

osteoblasts
Osteoblasts
Military electronic countermeasures
extracellular matrix
growth factors
Adsorption
Extracellular Matrix
Intercellular Signaling Peptides and Proteins
adsorption
Craniosynostoses
bone morphogenetic proteins
Bone Morphogenetic Protein 2
protein binding
transforming growth factor beta 1
Protein Binding
Transforming Growth Factor beta
sutures
Fusion reactions
Cranial Sutures
Dura Mater

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Differential growth factor adsorption to calvarial osteoblast-secreted extracellular matrices instructs osteoblastic behavior. / Bhat, Archana; Boyd, Simeon; Senders, Craig W; Leach, Jonathan K.

In: PLoS One, Vol. 6, No. 10, e25990, 05.10.2011.

Research output: Contribution to journalArticle

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