Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q9UIJ5 (Rec)
 58,342 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was designed to clarify the effects of bisphosphonate (BP) administration on structure and functions of osteoclasts in alveolar bone resorption during experimental movement of rat molars. To produce orthodontic force, elastic band was inserted between the upper first and second molars for 4 days, and dissected maxillae were then examined by means of light and electron microscopic immunocytochemistry for vacuolar-type H(+)-ATPase and lysosomal cystein proteinase, cathepsin K in osteoclasts. Vacuolar-type H(+)-ATPase and cathepsin K in osteoclasts are the most important enzymes for demineralization of apatite crystals and degradation of bone type-I collagen, respectively. At 1 day before elastic band insertion, BP was administered intraperitoneally. Control rats received the same volume of physiologic saline. In BP-administered rats, most osteoclasts exhibited either irregularly-formed ruffled borders and clear zones or only clear zones of various degrees of extension. Subcellular localization and expression of both vacuolar-type H(+)-ATPase and cathepsin K was significantly decreased in such osteoclasts with impaired ruffled borders and/or only clear zones by BP administration. In particular, cathepsin K secretion by osteoclasts towards resorption lacunae was markedly inhibited by BP administration. Our results indicate for the first time that BP administration significantly impair the osteoclast structure and reduces expression of both vacuolar-type H(+)-ATPase and cathepsin K in osteoclasts during tooth movement.
Anat Rec 2000 09 01
PMID:Bisphosphonate administration alters subcellular localization of vacuolar-type H(+)-ATPase and cathepsin K in osteoclasts during experimental movement of rat molars. 1096 38

Osteoprotegerin (OPG) is a novel secreted member of the tumor necrosis factor (TNF) receptor superfamily that negatively regulates osteoclastogenesis. The receptor activator of the NFKB ligand (RANKL) is one of the key regulatory molecules in osteoclast formation and binds to OPG. In this study, it was suggested that OPG and RANKL are involved in alveolar bone remodeling during orthodontic tooth movement. We examined RANKL localization and osteoclast induction in periodontal tissues during experimental movement of incisors in OPG-deficient mice. To produce orthodontic force, an elastic band was inserted between the upper right and left incisors for 2 or 5 days, and the dissected maxillae were examined for cytochemical and immunocytochemical localization of tartrate-resistant acid phosphatase (TRAP), vacuolar-type H(+)-ATPase, and RANKL. Compared to wild-type OPG (+/+) littermates, TRAP-positive multinucleated cells were markedly induced in the periodontal ligament (PDL) on the compressed side and in the adjacent alveolar bone of OPG-deficient mice. These multinucleated cells exhibited intense vacuolar-type H(+)-ATPase along the ruffled border membranes. Because of accelerated osteoclastic resorption in OPG-deficient mice, alveolar bone was severely destroyed and partially perforated at 2 and 5 days after force application. In both wild-type and OPG-deficient mice, RANKL expression became stronger at 2 and 5 days after force application than before force application. There was no apparent difference in intensity of RANKL expression between OPG (+/+) littermates and OPG-deficient mice. In both wild-type and OPG-deficient mice, expression of RANKL protein was detected in osteoblasts, fibroblasts, and osteoclasts mostly located in resorption lacunae. These results suggest that during orthodontic tooth movement, RANKL and OPG in the periodontal tissues are important determinants regulating balanced alveolar bone resorption.
Anat Rec 2002 04 01
PMID:Osteoclast induction in periodontal tissue during experimental movement of incisors in osteoprotegerin-deficient mice. 1192 Mar 84

The differentiation and functions of osteoclasts (OCs) are regulated by osteoblast-derived factors. Receptor activator of NFkB ligand (RANKL) is one of the key regulatory molecules in OC formation. Osteoprotegerin (OPG) is a novel secreted member of the TNF receptor superfamily that negatively regulates osteoclastogenesis and binds to RANKL. We examined the biological actions of macrophage-colony-stimulating factor (M-CSF), RANKL, and OPG on the differentiation of OCs isolated from cocultures of mouse osteoblastic cells and bone marrow cells. Preosteoclasts (pOCs) and OCs were characterized by their ultrastructure and the expression of OC markers such as tartrate-resistant acid phosphatase (TRAP) and vacuolar-type H(+)-ATPase. pOCs formed without any additives expressed TRAP, but showed little resorptive activity on cocultured dentine slices. TRAP-positive pOCs treated with M-CSF began to fuse with each other, but lacked a ruffled border (RB) and showed almost no resorptive activity. pOCs treated with RANKL became TRAP-positive multinucleated cells, which expressed intense vacuolar-type H(+)-ATPase along the RB membranes and exhibited prominent resorptive activity. Such effects of RANKL on pOCs were completely inhibited by the addition of OPG. OPG inhibited RB formation in mature OCs and reduced their resorptive activity, and also induced apoptosis of some OCs. These results suggest that 1) RANKL induces differentiation of functional OCs from pOCs, 2) M-CSF induces macrophage-like multinucleated cells, but not OCs, 3) OPG inhibits RB formation and resorptive activity in mature OCs, 4) OPG also induces apoptosis of OCs, and 5) RANKL and OPG are, therefore, important regulators of not only the terminal differentiation of OCs but also their resorptive function.
Anat Rec 2002 Oct 01
PMID:Regulation of osteoclast differentiation and function by receptor activator of NFkB ligand and osteoprotegerin. 1222 20

We examined the effects of long-term bisphosphonate (BP, pamidronate) administration at a therapeutic dose (1.5 mg/kg/day) on the distribution, structure, and vacuolar-type H(+)-ATPase expression of osteoclasts, and the resulting trabecular bone volume and structure in ovariectomized (OVX) mature rats. Six-month-old female rats were allocated to sham-operated control, untreated-OVX, and BP-administered OVX groups. Postoperatively, BP was administered intraperitoneally once a day to OVX rats for up to 30 days. On postoperative days 14, 30, and 60, all of the rats were killed and the distal metaphyseal area of the dissected humeri was examined. Quantitative backscattered-electron image analysis revealed that the trabecular bone volume/unit medullary area in untreated OVX rats was significantly (P < 0.05) lower than that in sham-operated controls at 30 and 60 days postoperation. BP administration significantly (P < 0.05) increased trabecular bone volume at 14, 30, and 60 days postoperation in BP-administered OVX rats compared to both sham-operated and untreated OVX rats. Compared to untreated OVX rats, the number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts along the bone trabeculae in BP-administered OVX rats was not significantly decreased on days 14 and 30, but was significantly decreased on day 60. Ultrastructurally, BP administration caused the disappearance of both the ruffled border (RB) and the clear zone (CZ) structures, and decreased the expression of vacuolar-type H(+)-ATPase in most osteoclasts, but did not significantly induce apoptosis of osteoclasts detected by the terminal dUTP nick end-labeling (TUNEL) method. Our results suggest that long-term BP administration significantly reduces bone and calcified cartilage resorption through impairment of the structure and bone-resorbing function of osteoclasts, and thereby effectively maintains trabecular bone volume and structure in ovariectomy-induced acute estrogen deficiency in mature rats.
Anat Rec A Discov Mol Cell Evol Biol 2003 Sep
PMID:Cellular mechanism of inhibition of osteoclastic resorption of bone and calcified cartilage by long-term pamidronate administration in ovariectomized mature rats. 1292 92