Yonsei Med J.  2003 Aug;44(4):593-601. 10.3349/ymj.2003.44.4.593.

The Effects of Recombinant Human BMP-7, Prepared from a COS-7 Expression System, on the Proliferation and Differentiation of Rat Newborn Calvarial Osteoblasts

Affiliations
  • 1Department of Medical Engineering, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul, Korea. parkjc@yumc.yonsei.ac.kr
  • 2Department of Orthopedic Surgery, Yonsei University College of Medicine, Seoul, Korea.

Abstract

A family of proteins, the bone morphogenetic proteins (BMPs), which promote osteoblast differentiation and bone mineralization, have recently been identified. One, BMP-7, has shown the ability to induce cartilage and bone formation processes. In this report, the possibility that other cell lines, to CHO cells, may also be available as host cells for the expression of hBMP-7 was validated. Recombinant human BMP (rhBMP) -7 was produced in COS-7 cells, as a processed mature disulfide-linked homodimer, with an apparent molecular weight of 36, 000. Examination of the expressions of the markers characteristic of osteoblast phenotypes showed that the rhBMP-7 specifically stimulated the inductions of alkaline phosphatase (ALP) (5-fold increase at 100 ng of rhBMP-7/ml), parathyroid hormone (PTH) -mediated intracellular cAMP production (4-fold increase at 100 ng of rhBMP-7/ml) and osteocalcin synthesis (5-fold increase at 100 ng of rhBMP-7/ml). In summary, the in vitro mineralization assay results provide evidence that the rhBMP-7 peptide, produced by COS-7 expression system, possesses intact biological activity. A similar pattern of biological activity was observed for the BMP-7 in COS-7 cells compared to the corresponding CHO cell expression system. Thus, these findings can be experimentally utilized for the production of rhBMPs for in vitro or in vivo studies.

Keyword

Bone morphogenetic protein; COS-7; rat newborn calvaria cell; osteoblast; DNA synthesis; alkaline phosphatase; cAMP; osteocalcin

MeSH Terms

Animals
Animals, Newborn
Bone Morphogenetic Proteins/*pharmacology
COS Cells
Cell Differentiation/drug effects
Cell Division/drug effects
Cells, Cultured
Human
Osteoblasts/*cytology
Rats
Rats, Sprague-Dawley
Recombinant Proteins/pharmacology
Skull/*cytology
Support, Non-U.S. Gov't
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