Noggin regulation of bone morphogenetic protein (BMP) 2/7 heterodimer activity in vitro

Wei Zhu, Jaehon Kim, Christina Cheng, Bernard A. Rawlins, Oheneba Boachie-Adjei, Ronald Crystal, Chisa Hidaka

Research output: Contribution to journalArticle

99 Citations (Scopus)

Abstract

Bone morphogenic proteins (BMPs) are growth factors important for skeletal development and bone growth. Noggin, one of the soluble BMP antagonists, regulates the action of BMPs on mesenchymal precursor cells, partially through a feedback type of inhibition. In this study, we constructed a novel BMP2/7 'fusion gene' that encodes both BMP2 and BMP7 genes in tandem by a linker. Polymerase chain reaction (PCR) and Western blotting showed that the BMP2/7 fusion gene construct led to the production of BMP2/7 heterodimers in A549 'producer' cells. When applied to C2C12 myoblastic cells, BMP2/7 heterodimers increased alkaline phosphatase (ALP) activity and osteocalcin (OCN) expression (markers of osteoblastic differentiation) more effectively than either BMP2 or BMP7 homodimers. Moreover, this heterodimer induced significantly lower levels of Noggin expression in C2C12 cells than respective homodimers at similar doses. The addition of Noggin did not affect the heterodimer's activities in increasing osteoblastic differentiation in C2C12 cells. In contrast, BMP2 and BMP7 homodimers were largely inhibited by Noggin. Our finding suggests that the 'fusion gene' construct led to the production of bioactive BMP2/7 heterodimers, which were not antagonized by Noggin as effectively as it to BMP homodimers. The weaker Noggin antagonism on BMP heterodimers compared to homodimers may contribute to increased osteogenic potency of heterodimers in vitro and in vivo.

Original languageEnglish
Pages (from-to)61-71
Number of pages11
JournalBone
Volume39
Issue number1
DOIs
Publication statusPublished - 1 Jul 2006
Externally publishedYes

Fingerprint

Bone Morphogenetic Protein 7
Bone Morphogenetic Protein 2
Bone Morphogenetic Proteins
Gene Fusion
Bone and Bones
Bone Development
Osteocalcin
Differentiation Antigens
Alkaline Phosphatase
Intercellular Signaling Peptides and Proteins
Proteins
Western Blotting
Polymerase Chain Reaction
In Vitro Techniques
Genes

Keywords

  • Bone morphogenetic protein
  • Fusion gene
  • Homodimer and heterodimer
  • Noggin
  • Osteoblastic differentiation

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Histology

Cite this

Zhu, W., Kim, J., Cheng, C., Rawlins, B. A., Boachie-Adjei, O., Crystal, R., & Hidaka, C. (2006). Noggin regulation of bone morphogenetic protein (BMP) 2/7 heterodimer activity in vitro. Bone, 39(1), 61-71. https://doi.org/10.1016/j.bone.2005.12.018

Noggin regulation of bone morphogenetic protein (BMP) 2/7 heterodimer activity in vitro. / Zhu, Wei; Kim, Jaehon; Cheng, Christina; Rawlins, Bernard A.; Boachie-Adjei, Oheneba; Crystal, Ronald; Hidaka, Chisa.

In: Bone, Vol. 39, No. 1, 01.07.2006, p. 61-71.

Research output: Contribution to journalArticle

Zhu, W, Kim, J, Cheng, C, Rawlins, BA, Boachie-Adjei, O, Crystal, R & Hidaka, C 2006, 'Noggin regulation of bone morphogenetic protein (BMP) 2/7 heterodimer activity in vitro', Bone, vol. 39, no. 1, pp. 61-71. https://doi.org/10.1016/j.bone.2005.12.018
Zhu, Wei ; Kim, Jaehon ; Cheng, Christina ; Rawlins, Bernard A. ; Boachie-Adjei, Oheneba ; Crystal, Ronald ; Hidaka, Chisa. / Noggin regulation of bone morphogenetic protein (BMP) 2/7 heterodimer activity in vitro. In: Bone. 2006 ; Vol. 39, No. 1. pp. 61-71.
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