Interaction between effects of parathyroid hormone and bisphosphonate on regulation of osteoclast activity by the osteoblast-like cell line UMR-106

Yu, Xinran; Schøller, Jørgen; Foged, Niels T.

doi:10.1016/s8756-3282(96)00184-6

Cited by 35 publications

(21 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…They have been suggested to inhibit differentiation, survival, and activity of osteoclast through osteoblastsecreted osteoclast-inhibiting factor, which has not yet been identified (Vitte et al, 1996;Yu et al, 1996). Recently, Mackie et al reported that pamidronate reduced RANKL mRNA expression in UMR-106 osteosarcoma cell line after a 6-day culture, but did not alter OPG expression, which is different from our results (Mackie et al, 2001).…”

Section: Resultscontrasting

confidence: 99%

Inhibitory action of bisphosphonates on bone resorption does not involve the regulation of RANKL and OPG expression

Kim

Kim²,

Baek³

2002

Exp Mol Med

View full text Add to dashboard Cite

show abstract

Section: Resultscontrasting

confidence: 99%

Inhibitory action of bisphosphonates on bone resorption does not involve the regulation of RANKL and OPG expression

Kim

Kim²,

Baek³

2002

Exp Mol Med

View full text Add to dashboard Cite

show abstract

“…Vitté and colleagues (Vitté et al, 1996) and Sahni et al (1993) hypothesized that bisphosphonates affect osteoclast differentiation, survival and activity via osteoblast-produced intermediaries but did not identify these compounds. Yu et al subsequently demonstrated that UMR 106 cells express an osteoclast-inhibiting factor following bisphosphonate exposure and an osteoclast-stimulating factor after parathyroid hormone exposure (Yu et al, 1996). This supports the possibility that an imbalance in the relative expression of the osteoclast regulating genes by UMR 106 following bisphosphonate exposure might be responsible for the functional osteoclast impairment.…”

Section: -20%mentioning

confidence: 89%

Bisphosphonates regulate cell growth and gene expression in the UMR 106-01 clonal rat osteosarcoma cell line

et al. 2001

View full text Add to dashboard Cite

Despite significant improvements in patient survival and local disease control, 25% of patients with osteosarcoma develop metastases and the surgery for many extremity lesions still includes amputation. Thus, modalities that inhibit tumour growth and the metastatic cascade will have a significant impact on patient survival and potential for limb sparing surgery.Tumours induce bone destruction by cellular processes, such as osteoclast-mediated bone lysis. The importance of osteoclastmediated lysis has been demonstrated in other malignancies, where the development of osseous metastases has been shown to be mediated by soluble tumour-related osteoclast activating factors (Galasko, 1976). More recently, the induction of specific osteoclast recruiting factors in osteoblasts/stromal cells following contact with myeloma and breast cancer cells has been demonstrated (Chikatsu et al, 2000). Bisphosphonates have recognized efficacy in reducing bone destruction, pain and pathological fracture in a variety of lytic primary and metastatic diseases of the skeleton (Thiébaud et al, 1991;Coleman and Purohit, 1993;Shipman et al, 1997;Bloomfield, 1998;Diel et al, 1998). They have more recently been shown to inhibit establishment and growth of prostate cancer metastases, which are generally considered to be osteoblastic in their growth pattern (Adami, 1997). We proposed that, as with the intraosseous growth of prostate cancer, the local spread of osteosarcoma involves proteolytic and osteoclast-mediated bone destruction. The bisphosphonates may reduce bone destruction by uncoupling close regulation of osteoclast activity by osteoblast-like cells.The aims of our study were to examine the effects on the regulation of proliferation and apoptosis by bisphosphonate treatment of a clonal osteosarcoma cell line. Further, we assessed the expression of an osteoclast differentiating factor, receptor activator of NF-κβ (RANKL) (Yasuda et al, 1998b) and an osteoclastogenesis inhibitory factor, osteoprotegerin (OPG) (Simonet et al, 1997;Yasuda et al, 1998a). Finally, we investigated the effects on osteoblast-related gene expression by an aminobisphosphonate and a non-aminobisphosphonate. The use of a bisphosphonate from each group allows comparison of their relative potencies with the known effects on osteoclasts and bone resorption studies (Fleisch, 1993). MATERIALS AND METHODS Cell cultureUMR 106-01 cells derived from a 32 P-induced osteosarcoma in rats (Martin et al, 1976) were used. Cells were cultured in 75 cm 2 tissue culture flasks (Greiner Cellstar) in α-modified Minimal Essential Medium (α-MEM) containing hepes 4 g l Ϫ1 , sodium bicarbonate 1.95 g 6 Ϫ1 , gentamicin 80 mg 6 Ϫ1 , pH 7.4 and 10% fetal bovine serum (FBS), incubated at 37˚C and equilibrated in 5% CO 2 in air. Subcultures were performed using 0.0125% trypsin in 0.5 mM Na 2 EDTA in calcium and magnesium-free phosphate buffer (1 ϫ versene) to harvest the cells. Summary Local growth of osteosarcoma involves destruction of host bone by proteolytic mechanisms and/or host osteocl...

show abstract

“…Since autoradiography showed that '251-VIP binding sites were present only on stromal cells and not on osteoclasts, it is conceivable that the inhibitory effect of VIP and the two PACAPs on osteoclastic bone resorption is mediated not by a direct effect on the osteoclasts but rather by a stromal cell-derived inhibitory factor, previously found to be secreted by osteoblastic cells in response to a bisphosphonate (Yu, Sch0ller & Foged, 1996 In addition to the finding of binding sites for PACAP/VIP in osteoblastic cells (Hohmann & Tashjian, 1984;Bjurholm et al 1992; Lerner et al 1994), the present study proposes that osteoblasts, or perhaps other stromal cells, may produce an inhibitory factor for osteoclastic bone resorption in vitro. Combined with the presence of nerve fibres immunoreactive for VIP in the bone compartments (Bjurholm et al 1988(Bjurholm et al , 1989Hohmann et al 1986), it is likely that VIP, and probably also PACAP-38 and PACAP-27, are involved in the local regulation of bone cell metabolism in vivo.…”

Section: Bone Resorptionmentioning

confidence: 99%

Pituitary adenylyl cyclase‐activating polypeptides and vasoactive intestinal peptide inhibit bone resorption by isolated rabbit osteoclasts

Winding¹,

Wiltink²,

Foged³

1997

Experimental Physiology

View full text Add to dashboard Cite

SUMMARYNerve fibres present in the periosteum, cortical bone and bone marrow are proposed to be involved in the regulation of bone metabolism by the release of neuropeptides acting locally on bone cells. The present study describes the effects of vasoactive intestinal polypeptide (VIP), shown to be present in the vicinity of bone, and the two related neuropeptides pituitary adenylyl cyclaseactivating polypeptide(1-38) (PACAP-38) and PACAP-27 on bone resorption in vitro induced by osteoclasts isolated from 10-day-old rabbits. Bone resorption was measured as the number and total area of pits formed by tartrate-resistant acid phosphatase-positive multinucleated cells (TRAP+ MNCs) cultured for 3 days on devitalized slices of bovine cortical bone. All three neuropeptides had significant inhibitory effects on both the number and area of pits formed. Trifluoperazine and mellitin, two selective calmodulin inhibitors, failed to block the VIP-induced inhibition of bone resorption. Our results demonstrate a non-toxic and probably stromal cellderived effect of PACAP-38, PACAP-27 and VIP on isolated rabbit osteoclasts, resulting in a potent inhibition of bone resorption in vitro. The signal transduction pathway for inhibition induced by PACAP-38, PACAP-27 and VIP may be mediated partly by changes in intracellular Ca2+ in stromal cells.

show abstract

Interaction between effects of parathyroid hormone and bisphosphonate on regulation of osteoclast activity by the osteoblast-like cell line UMR-106

Cited by 35 publications

References 18 publications

Inhibitory action of bisphosphonates on bone resorption does not involve the regulation of RANKL and OPG expression

Inhibitory action of bisphosphonates on bone resorption does not involve the regulation of RANKL and OPG expression

Bisphosphonates regulate cell growth and gene expression in the UMR 106-01 clonal rat osteosarcoma cell line

Pituitary adenylyl cyclase‐activating polypeptides and vasoactive intestinal peptide inhibit bone resorption by isolated rabbit osteoclasts

Contact Info

Product

Resources

About