Calcium-Sensing Receptor in Mature Osteoclasts, Which Are Bone Resorbing Cells

Kameda, Takashi; Miyata, Hiroshi; Yamada, Yoshiji; Takai, Hiroyuki; Amizuka, Norio; Kobori, Masato; Izumi, Noriaki; Kawashima, Hiroyuki; Ozawa, Hiroki; Ikeda, Kyoji; Kameda, A; Hakeda, Yoshiyuki; Kumegawa, Masayoshi

doi:10.1006/bbrc.1998.8448

Cited by 198 publications

(126 citation statements)

References 17 publications

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Section: Introductionmentioning

confidence: 99%

“…The CaSR belongs to the type III family of G-proteincoupled receptors, which comprises the metabotropic glutamate receptor and putative vomeronasal organ receptors (Brown et al, 1993). Several lines of evidence have suggested that an increase in local Calcium sensing receptor form s com plex with and is up-regulated by caveolin-1 in cultured hum an osteosarcom a (Saos-2) cells calcium concentration in the resorption lacunae suppresses osteoclastic bone-resorbing activity through an increase in intracellular calcium; this is mediated through a ryanodine-like receptor (Zaidi et al, 1989;1991;1993;Adebanjo et al, 1994;Shin et al, 2003) and the CaSR regulates osteoclastic bone resorption (Kameda et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

“…Vol. 37(2), [91][92][93][94][95][96][97][98][99][100] 2005 calcium concentration in the resorption lacunae suppresses osteoclastic bone-resorbing activity through an increase in intracellular calcium; this is mediated through a ryanodine-like receptor (Zaidi et al, 1989;1991;1993;Adebanjo et al, 1994;Shin et al, 2003) and the CaSR regulates osteoclastic bone resorption (Kameda et al, 1998).Caveolae are plasma membrane organelles that are characterized by a low solubility in Triton X-100 and these are the organelles where specific lipid and protein components are subcompartmentalized (Kurzchalia and Parton, 1999). Caveolin (Cav), a 21-to 24-kDa integral membrane protein, is a principal component of the caveolae membrane and it exists as several isoforms (Cav-1, -2, and -3) (Okamoto et al, 1998;Kurzchalia and Parton, 1999).…”

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Calcium sensing receptor forms complex with and is up-regulated by caveolin-1 in cultured human osteosarcoma (Saos-2) cells

Jung

Kwak²,

Kim³

et al. 2005

Exp Mol Med

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A bstractThe calcium sensing receptor (C aSR ) plays an im portant role for sensing local changes in the extracellular calcium concentration ([C a 2+ ] o ) in bone rem odeling. A lthough the function of C aSR is know n, the regulatory m echanism of C aSR rem ains controversial. W e report here the regulatory effect of caveolin on C aSR function as a process of C aSR regulation by using the hum an osteosarcom a cell line (Saos-2). The intracellular calcium concentration ([C Keyw ords: antisense oligodeoxynucleotides; calcium sensing receptor; caveolae; caveolin-1; confocal microscopy; osteosarcoma cell linea IntroductionExtracellular calcium is essential for a number of vital processes, including bone mineralization, blood coagulation, regulation of enzymatic activity, and the modulation of permeability and excitability of the plasma membranes. For these reasons, the calcium concentration in extracellular fluids is under strict control by a complex homeostatic system that includes the bones, kidney, intestines, parathyroid and thyroid glands (Brown, 1991). The extracellular calcium sensing receptor (CaSR) is an essential component of this system for regulating parathyroid hormone secretion, Ca 2+ excretion by the kidney and bone remodeling. The CaSR belongs to the type III family of G-proteincoupled receptors, which comprises the metabotropic glutamate receptor and putative vomeronasal organ receptors (Brown et al., 1993). Several lines of evidence have suggested that an increase in local Calcium sensing receptor form s com plex with and is up-regulated by caveolin-1 in cultured hum an osteosarcom a (Saos-2) cells 92 Exp. Mol. Med. Vol. 37(2), [91][92][93][94][95][96][97][98][99][100] 2005 calcium concentration in the resorption lacunae suppresses osteoclastic bone-resorbing activity through an increase in intracellular calcium; this is mediated through a ryanodine-like receptor (Zaidi et al., 1989;1991;1993;Adebanjo et al., 1994;Shin et al., 2003) and the CaSR regulates osteoclastic bone resorption (Kameda et al., 1998).Caveolae are plasma membrane organelles that are characterized by a low solubility in Triton X-100 and these are the organelles where specific lipid and protein components are subcompartmentalized (Kurzchalia and Parton, 1999). Caveolin (Cav), a 21-to 24-kDa integral membrane protein, is a principal component of the caveolae membrane and it exists as several isoforms (Cav-1, -2, and -3) (Okamoto et al., 1998;Kurzchalia and Parton, 1999). Recent studies have shown that functional proteins including receptors are localized in the caveolae by being anchored through the caveolins (Li et al., 1995; GarciaCardena et al., 1996;Couet et al., 1997;Lee et al., 2001;Cha et al., 2004). In bone, there is no evidence of the interaction between caveolin and CaSR, and for the regulatory effect of caveolin on CaSR function.The purpose of present study, therefore, is to demonstrate the relationship between CaSR and caveolins in the osteosarcoma cell line (Saos-2). Our results show that CaSR protein is co-locali...

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Calcium sensing receptor forms complex with and is up-regulated by caveolin-1 in cultured human osteosarcoma (Saos-2) cells

Jung

Kwak²,

Kim³

et al. 2005

Exp Mol Med

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“…Increasing evidence has suggested that CASR is expressed in stromal cell, preosteoclasts, mature osteoclasts, and various osteoblastic cell lines and may have an important function in bone cells (7,23,24,25,26). ALP has been recognized as a bone turnover marker.…”

Section: Discussionmentioning

confidence: 99%

Clinical phenotypes of Chinese primary hyperparathyroidism patients are associated with the calcium-sensing receptor gene R990G polymorphism

Han

Wang

Nie

et al. 2013

European Journal of Endocrinology

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Objective: The purpose of this study was to investigate the distribution of the A986S and R990G polymorphisms of the calcium-sensing receptor (CASR) gene in the Chinese population and whether there is an association between genetic variants and the risk of developing primary hyperparathyroidism (PHPT) and its associated clinical phenotypes. Methods: A total of 164 Chinese Han PHPT patients (M/F: 51/113) and 230 healthy controls (M/F: 50/180) were enrolled. The common clinical parameters of PHPT patients including biochemical markers, bone mineral density (BMD), kidney stone occurrence, and pathology results were analyzed. Genotyping was conducted for both the patients and controls, and it was carried out using standard procedures. Results: The R990G variant was more frequently present than the A986S variant in this group of Chinese PHPT patients. The R allele increased the risk of PHPT (odds ratioZ1.134, 95% CI: 1.008, 1.277, and PZ0.036). Patients with either the RR or RG genotype had lower blood calcium levels and higher alkaline phosphate levels than patients with the GG genotype. The lumbar BMD T-score was K2.20 (K2.63, K0.32) in patients with the GG genotype, and it was significantly lower in patients with the RRCRG genotype (K2.53 (K3.70, K1.72) PZ0.036). Patients with the R allele had a significantly higher incidence of hyperplasia (25.0%) and carcinomas (7.1%) than those with the GG genotype (5.3 and 0% respectively; PZ0.025). The prevalence of osteoporosis and parathyroid carcinomas was higher in Chinese PHPT patients with the R allele. Conclusion: The R990G polymorphism is most frequently present in the Chinese population and among patients with PHPT. Additional studies in the Chinese population are needed to elaborate the relationship between genetics and PHPT.

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“…It remains uncertain as to whether the RyR-2 also itself functions as the Ca 2+ sensor, conceivably through its intraluminal low-affinity Ca 2+ binding site [Anderson et al, 1989] or is coupled to a distinct intramembrane entity of the conventional 7-pass G-protein coupled types described elsewhere [Kameda et al, 1998]. The mechanism by which such a surface event would induce a release of intracellularly stored Ca 2+ remains unclear.…”

Section: Is Ca 2+ Sensing Coupled To Changes In Cytosolic [Ca 2+ ]?mentioning

confidence: 99%

Calcium Signalling and Calcium Transport in Bone Disease

Blair

Schlesinger

Huang

et al.

Subcellular Biochemistry

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Calcium transport and calcium signalling mechanisms in bone cells have, in many cases, been discovered by study of diseases with disordered bone metabolism. Calcium matrix deposition is driven primarily by phosphate production, and disorders in bone deposition include abnormalities in membrane phosphate transport such as in chondrocalcinosis, and defects in phosphate-producing enzymes such as in hypophosphatasia. Matrix removal is driven by acidification, which dissolves the mineral. Disorders in calcium removal from bone matrix by osteoclasts cause osteopetrosis. On the other hand, although bone is central to management of extracellular calcium, bone is not a major calcium sensing organ, although calcium sensing proteins are expressed in both osteoblasts and osteoclasts. Intracellular calcium signals are involved in secondary control including cellular motility and survival, but the relationship of these findings to specific diseases is not clear. Intracellular calcium signals may regulate the balance of cell survival versus proliferation or anabolic functional response as part of signalling cascades that integrate the response to primary signals via cell stretch, estrogen, tyrosine kinase, and tumor necrosis factor receptors Keywords Hypophosphatasia; chondrocalcinosis; osteopetrosis; osteoporosis Although bone is not considered a major calcium sensing organ in humans, the cells of bone tissue control over 99% of the human body's calcium content. The principal calcium sensors that regulate bone calcium uptake and release are in the parathyroid glands. Bone function is also modified by vitamin D and by calcium transport in the kidney and intestine. These indirect mechanisms of controlling bone calcium metabolism are beyond the scope of our considerations here. In spite of processing such massive quantities of the Ca 2+ bone cells use calcium in their homeostatic control processes. The massive movement of calcium is carried out by specialized and regulated transporters. Defects in the transporters cause diseases with affect bone structure or function. Indeed, inborn errors have been very important in defining the calcium transport mechanisms in bone.Additionally, calcium is used by bone forming and bone degrading cells as a secondary mediator of hormone and cytokine action. These actions include roles in intercellular communication within groups of osteoblasts, which are connected by gap junctions [Henriksen et al., 2006]. These osteoblast groups function in a coordinated fashion in bone synthesis and maintenance, and are collectively known as the osteon. Osteoblasts in these groups are connected by gap junctions which are capable of propagating signals in the cell groups, including calcium waves [Xia and Ferrier, 1992]. Calcium is also an important regulator of

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Calcium-Sensing Receptor in Mature Osteoclasts, Which Are Bone Resorbing Cells

Cited by 198 publications

References 17 publications

Calcium sensing receptor forms complex with and is up-regulated by caveolin-1 in cultured human osteosarcoma (Saos-2) cells

Calcium sensing receptor forms complex with and is up-regulated by caveolin-1 in cultured human osteosarcoma (Saos-2) cells

Clinical phenotypes of Chinese primary hyperparathyroidism patients are associated with the calcium-sensing receptor gene R990G polymorphism

Calcium Signalling and Calcium Transport in Bone Disease

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