Osteoactivin acts as downstream mediator of BMP-2 effects on osteoblast function

Details

• Personal Author:
  Abdelmagid SM ; Arango-Hisijara I ; Barbe MF ; Owen TA ; Popoff SN ; Safadi FF
• Description:
  Our laboratory previously showed that osteoactivin (OA) is a novel, osteoblast-related glycoprotein that plays a role in osteoblast differentiation and function. The purpose of this study was to examine the regulation of OA expression by BMP-2 and the role OA plays as a downstream mediator of BMP-2 effects in osteoblast function. Using primary osteoblast cultures, we tested different doses of BMP-2 on the regulation of OA expression during osteoblast development. To test whether Smad-1 signaling is responsible for BMP-2 regulation of OA expression, osteoblast cultures were transfected with Smad1 siRNA, treated with 50 ng/ml of BMP-2 and analyzed by Western blot. BMP-2 treatment increased OA mRNA and protein expression in a dose-dependent manner and this upregulation was blocked in Smad1 siRNA transfected cultures. We next examined whether the role of OA as a downstream mediator of BMP-2 effects on osteoblast differentiation and matrix mineralization. Osteoblast cultures were transfected with OA antisense oligonucleotides and treated with 50 ng/ml of BMP-2. Cultures transfected with OA antisense oligonucleotides and treated with BMP-2 showed a reduction of OA expression associated with a significant reduction in early and late differentiation markers induced by BMP-2. Therefore, OA acts, at least in part, as a downstream mediator of BMP-2 effects on osteoblast differentiation and matrix mineralization. Our findings suggest that BMP-2 regulates OA expression through the Smad1 signaling pathway. Our data also emphasize that OA protein acts as a downstream mediator of BMP-2 effects on osteoblast differentiation and function. [Description provided by NIOSH]
• Subjects:
  Animals Cytology Energy Metabolism Genetics Laboratories Musculoskeletal System Occupational Health Safety
• Keywords:
  Bone-structure Dose-response Drug-interaction Glycoproteins Laboratory-animals Metabolism Osteogenesis Pharmacology Proteins Tissue-culture
• ISSN:
  0021-9541
• Document Type:
  Text
• Funding:
  Cooperative Agreement
• Genre:
  Journal Article
• Place as Subject:
  Connecticut ; OSHA Region 1 ; OSHA Region 3 ; Pennsylvania
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  26-37
• Volume:
  210
• Issue:
  1
• NIOSHTIC Number:
  nn:20041716
• Citation:
  J Cell Physiol 2007 Jan; 210(1):26-37
• Contact Point Address:
  Dr. Fayez F. Safadi, Associate Professor, Department of Anatomy and Cell Biology, Temple University School of Medicine, 3400 North Broad Street, Philadelphia, PA 19140
• Email:
  fsafadi@temple.edu
• Federal Fiscal Year:
  2007
• Performing Organization:
  Temple University, Philadelphia, Pennsylvania
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  Journal of Cellular Physiology
• End Date:
  20080630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:aa87810765fdf80de3cd2a09439f9d2332899813329f0d53185be765e54cb05b2ea51b8d2551addb6ae1069690a63ba85b4e8b91404061478ab423efb115a0f8
• Download URL:
  https://stacks.cdc.gov/view/cdc/194205/cdc_194205_DS1.pdf
• File Type:
  [PDF - 577.62 KB ]