title: Bone morphogenic protein-2 induces apoptosis and cytotoxicity in periodontal ligament cells.
abstract: BACKGROUND
  Periodontal ligament (PDL) expresses endogenous growth factors, such as bone morphogenic proteins (BMPs), which facilitate maintenance of tissue homeostasis. Inflammatory conditions, such as chronic periodontitis, could disrupt this homeostasis, and physiologic levels of growth factors may be insufficient to maintain tissue homeostasis. BMPs facilitate periodontal bone regeneration but also are implicated in causing tooth ankylosis and root resorption. The underlying mechanism of tooth ankylosis is unclear. However, there is evidence that BMPs induce apoptosis in progenitor cells. Little is known about BMP-induced cytotoxicity in PDL cells, which contain a population of progenitor cells. The aim of this study is to determine BMP2-induced osteogenic mediators and cytotoxic effects in PDL cells and compare these cells to osteoblasts.
  
  
  METHODS
  Human PDL cells and primary osteoblasts were stimulated with doses of 1 to 200 ng/mL BMP2. Expression of alkaline phosphatase (ALP), in vitro mineralization along with osteonectin expression, induction of apoptosis, and cytotoxicity assays were performed.
  
  
  RESULTS
  PDL cells and osteoblasts upregulated ALP and in vitro mineralization in a dose-dependent manner with BMP2 stimulation. However, at BMP2 concentrations >10 ng/mL, ALP, in vitro mineralization, and osteonectin were downregulated in PDL cells. Relative to osteoblasts, PDL cells were susceptible to apoptosis and cytotoxicity with 10 times lower concentration of BMP2.
  
  
  CONCLUSIONS
  Relative to osteoblasts, PDL cells are susceptible to BMP2-induced cytotoxicity. BMP-induced tooth ankylosis is controversial and is poorly understood. Disruption of PDL homeostasis by BMP-induced apoptosis could play a role in tooth ankylosis.
authors: Department of Periodontics, University of Washington, Seattle, WA 98195-7444, USA. manojm@u.washington.edu
authors: Manoj
authors: M
authors: Muthukuru
mesh_terms: D000469:Alkaline Phosphatase / Q000032:analysis / Q000187:drug effects; D017209:Apoptosis / Q000187:drug effects*; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors; D002113:Calcification, Physiologic / Q000187:drug effects; D002118:Calcium / Q000032:analysis; D002352:Carrier Proteins / Q000032:analysis / Q000187:drug effects; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects; D047168:Cystine Knot Motifs / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005434:Flow Cytometry; D006801:Humans; D010006:Osteoblasts / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects; D015676:Osteonectin / Q000187:drug effects; D010513:Periodontal Ligament / Q000166:cytology / Q000187:drug effects*; D060888:Real-Time Polymerase Chain Reaction; D015854:Up-Regulation; D000099176:Noggin Protein
chemical_list: D000469:Alkaline Phosphatase; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D002118:Calcium; D002352:Carrier Proteins; D015676:Osteonectin; D000099176:Noggin Protein; C525718:BMP2 protein, human