title: Force-induced osteoclast apoptosis in vivo is accompanied by elevation in transforming growth factor beta and osteoprotegerin expression.
abstract: The mechanism controlling the disappearance of osteoclasts from bone surfaces after bone resorption in vivo is largely unknown. This is because there is no suitable experimental system to trace the final fate of osteoclasts. Here, we used an experimental model of tooth movement in rats to show that preexisting osteoclasts disappeared from the bone surface through apoptosis during a force-induced rapid shift from bone resorption to formation. On the distal alveolar bone surface of the maxillary molar in growing rats, many mature osteoclasts were present. When light tensional force was applied to the bone surface through an orthodontic appliance, these preexisting osteoclasts gradually disappeared. One day after the application of force, about 24% of the osteoclasts exhibited apoptotic morphology and the proportion of apoptotic cells was increased to 41% by day 2, then decreased afterward. These changes were undetectable on the control distal alveolar bone surface, which is free from tensional force. As shown by in situ hybridization, a marked increase in transforming growth factor beta1 (TGF-beta1) and osteoprotegerin (OPG) messenger RNA (mRNA) was observed in the stretched cells on the tensioned distal bone surface, simultaneously with the loss of osteoclasts. Both of these factors are known to have a negative effect on osteoclast recruitment and survival. As early as 2 days after force application, some of these stretched cells were identified as cuboidal osteoblasts showing intense signals for both factors. Our data suggest there may be a sequential link in tensional force applied on the bone lining cells, up-regulation of TGF-beta1/OPG, and disappearance of osteoclasts.
authors.affiliation: Department of Orthodontics, Nagasaki University School of Dentistry, Sakamoto, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: F
authors.initials: F
authors.lastname: Hashimoto
authors.forename: H
authors.initials: H
authors.lastname: Miyamoto
authors.forename: K
authors.initials: K
authors.lastname: Kanaoka
authors.forename: Y
authors.initials: Y
authors.lastname: Miyazaki-Kawashita
authors.forename: T
authors.initials: T
authors.lastname: Nakashima
authors.forename: M
authors.initials: M
authors.lastname: Shibata
authors.forename: K
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Y
authors.initials: Y
authors.lastname: Kato
authors.forename: H
authors.initials: H
authors.lastname: Sakai
mesh_terms: D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001862:Bone Resorption / Q000139:chemically induced / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D056657:Cathepsin K; D002403:Cathepsins / Q000032:analysis; D002452:Cell Count; D002470:Cell Survival; D006023:Glycoproteins / Q000235:genetics* / Q000494:pharmacology; D006651:Histocytochemistry; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D007527:Isoenzymes / Q000378:metabolism; D008233:Lymphotoxin-alpha / Q000235:genetics*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D015675:Osteocalcin / Q000235:genetics / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D053244:Osteoprotegerin; D053245:RANK Ligand; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; D013314:Stress, Mechanical; D000071681:Tartrate-Resistant Acid Phosphatase; D014070:Tooth / Q000166:cytology / Q000254:growth & development / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D006023:Glycoproteins; D007527:Isoenzymes; D008233:Lymphotoxin-alpha; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D053245:RANK Ligand; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; C506032:Tnfrsf11b protein, rat; D015675:Osteocalcin; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D002403:Cathepsins; D056657:Cathepsin K; C534133:Ctsk protein, rat