Proenkephalin A in bone-derived cells

Haim Rosen, Roberto D. Polakiewicz, Simone Benzakine, Zvi Bar-Shavit*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

34 Scopus citations


Enkephalins, a group of small peptides with opiate-like activity, have been defined originally as neuropeptides. Recent reports showed, using in situ hybridization, that the enkephalin-encoding gene, proenkephalin A (pEnkA), is expressed in nondifferentiated cells of diverse mesodermal lineages. The transient expression of pEnkA in these tissues during organogenesis suggests that this gene is involved in processes such as differentiation and/or cell proliferation. In situ hybridization revealed that bone and cartilage are among the tissues that express pEnkA most actively during organogenesis. Here we show that pEnkA mRNA is abundant in normal calvaria-derived cells and in osteosarcoma-derived cell lines ROS 17/2.8 and ROS 25/1. In addition, pEnkA-derived peptides are synthesized and secreted by these cells, as revealed by specific RIA. pEnkA expression in ROS cells is decreased by osteogenin, an osteoinductive factor, and by the calcium-regulating hormone, 1,25-dihydroxyvitamin D3, whereas the osteoblastic phenotype marker, alkaline phosphatase, is increased by these factors. These results together with the inhibitory effects of pEnkA-derived peptides on alkaline phosphatase activity in ROS 17/2.8 cells suggest that pEnkA is involved in bone development and provide a model system for further analysis of pEnkA expression during this process.

Original languageAmerican English
Pages (from-to)3705-3709
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number9
StatePublished - 1991
Externally publishedYes


  • Alkaline phosphatase
  • Bone development
  • Gene expression
  • Opioids
  • Osteoblasts


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