Article: The cross-talk between osteoclasts and osteoblasts in response to strontium treatment: involvement of osteoprotegerin
| Title | The cross-talk between osteoclasts and osteoblasts in response to strontium treatment: involvement of osteoprotegerin | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Authors | Peng, S1 2 3 Liu, XS2 Huang, S3 Li, Z3 Pan, H3 Zhen, W1 Luk, KDK3 Guo, XE2 Lu, WW3 | ||||||||
| Issue Date | 2011 | ||||||||
| Publisher | Elsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/bone | ||||||||
| Citation | Bone, 2011, v. 49 n. 6, p. 1290-1298 [How to Cite?] DOI: http://dx.doi.org/10.1016/j.bone.2011.08.031 | ||||||||
| Abstract | BACKGROUND: The mechanism for the uncoupling effects of Sr on bone remains to be evaluated. Osteoblasts play important roles in osteoclastogenesis through regulating receptor activated nuclear factor kappa B (RANK) ligand (RANKL) and osteoprotegerin (OPG) expression. We hypothesize that OPG plays an important role in the cross-talk between osteoclasts and osteoblasts in response to Sr treatment. MATERIALS AND METHODS: MC3T3E1 cells were treated with Sr chloride (0-3 mM) and conditioned media were collected at 24h after the treatment. The effect of conditioned media on osteoclastogenesis was evaluated by tartrate-resistant acid phosphatase (TRAP) staining and bone resorption pits analysis. OPG and RANKL mRNA expressions in osteoblastic cells and protein secretion in the conditioned media were analyzed with real-time PCR and ELISA assay, respectively. The role of OPG in Sr-mediated inhibition of osteoclastogenesis was further evaluated with anti-OPG antibody in pre-osteoclastic cells. The role of OPG in Sr-mediated uncoupling effects on osteoporotic bone was evaluated by an animal study. Ovariectomized rats were oral administrated with vehicle or Sr chloride for two months supplemented with anti-IgG antibody (control) or anti-OPG antibody. The effects of OPG neutralization after Sr treatment on bone metabolism were analyzed by microCT, bone histomorphometry and biochemical analysis. RESULTS: The conditioned media derived from Sr-treated osteoblastic cells exerted a dose-dependent inhibitory effect on osteoclastic differentiation and resorptive activity in pre-osteoclastic cells. OPG mRNA expression and protein secretion in osteoblastic cells were significantly increased after Sr treatment. Neutralization with anti-OPG antibody abolished the inhibitory effect of conditioned media on RANKL-induced osteoclastogenesis. The uncoupling effects of Sr treatment on trabecular bone were evidenced by greater bone volume and trabecular number, greater osteoid surface and bone formation rate, while less osteoclast surface. These effects were attenuated by the OPG neutralization by anti-OPG antibody injection. CONCLUSION: The evidences from the in vitro and in vivo studies suggested that OPG played an important role in the uncoupling effect of Sr on bone metabolism, possibly by acting as a cross-talk molecule between osteoclasts and osteoblasts in response to Sr treatment. | ||||||||
| ISSN | 8756-3282 2011 Impact Factor: 4.023 2011 SCImago Journal Rankings: 0.326 | ||||||||
| DOI | http://dx.doi.org/10.1016/j.bone.2011.08.031 | ||||||||
| ISI Accession Number ID | WOS:000297663500021
Funding Information: This study was supported by the Innovation and Technology Fund (ITF; Project ref. no. GHP/009/06), Hong Kong Research Grants Council (RGC) Grant 714908 and National Institutes of Health (R01 AR051376). | ||||||||
| References | References in Scopus | ||||||||
| Grants | Optimization and commercialization of strontium containing bioactive bone cement for various orthopaedic applications |
| dc.contributor.author | Peng, S | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| dc.contributor.author | Liu, XS | ||||||||
| dc.contributor.author | Huang, S | ||||||||
| dc.contributor.author | Li, Z | ||||||||
| dc.contributor.author | Pan, H | ||||||||
| dc.contributor.author | Zhen, W | ||||||||
| dc.contributor.author | Luk, KDK | ||||||||
| dc.contributor.author | Guo, XE | ||||||||
| dc.contributor.author | Lu, WW | ||||||||
| dc.date.accessioned | 2011-11-02T03:05:44Z | ||||||||
| dc.date.available | 2011-11-02T03:05:44Z | ||||||||
| dc.date.issued | 2011 | ||||||||
| dc.description.abstract | BACKGROUND: The mechanism for the uncoupling effects of Sr on bone remains to be evaluated. Osteoblasts play important roles in osteoclastogenesis through regulating receptor activated nuclear factor kappa B (RANK) ligand (RANKL) and osteoprotegerin (OPG) expression. We hypothesize that OPG plays an important role in the cross-talk between osteoclasts and osteoblasts in response to Sr treatment. MATERIALS AND METHODS: MC3T3E1 cells were treated with Sr chloride (0-3 mM) and conditioned media were collected at 24h after the treatment. The effect of conditioned media on osteoclastogenesis was evaluated by tartrate-resistant acid phosphatase (TRAP) staining and bone resorption pits analysis. OPG and RANKL mRNA expressions in osteoblastic cells and protein secretion in the conditioned media were analyzed with real-time PCR and ELISA assay, respectively. The role of OPG in Sr-mediated inhibition of osteoclastogenesis was further evaluated with anti-OPG antibody in pre-osteoclastic cells. The role of OPG in Sr-mediated uncoupling effects on osteoporotic bone was evaluated by an animal study. Ovariectomized rats were oral administrated with vehicle or Sr chloride for two months supplemented with anti-IgG antibody (control) or anti-OPG antibody. The effects of OPG neutralization after Sr treatment on bone metabolism were analyzed by microCT, bone histomorphometry and biochemical analysis. RESULTS: The conditioned media derived from Sr-treated osteoblastic cells exerted a dose-dependent inhibitory effect on osteoclastic differentiation and resorptive activity in pre-osteoclastic cells. OPG mRNA expression and protein secretion in osteoblastic cells were significantly increased after Sr treatment. Neutralization with anti-OPG antibody abolished the inhibitory effect of conditioned media on RANKL-induced osteoclastogenesis. The uncoupling effects of Sr treatment on trabecular bone were evidenced by greater bone volume and trabecular number, greater osteoid surface and bone formation rate, while less osteoclast surface. These effects were attenuated by the OPG neutralization by anti-OPG antibody injection. CONCLUSION: The evidences from the in vitro and in vivo studies suggested that OPG played an important role in the uncoupling effect of Sr on bone metabolism, possibly by acting as a cross-talk molecule between osteoclasts and osteoblasts in response to Sr treatment. | ||||||||
| dc.description.grant | Optimization and commercialization of strontium containing bioactive bone cement for various orthopaedic applications | ||||||||
| dc.description.grantcode | 96197 | ||||||||
| dc.description.nature | link_to_subscribed_fulltext | ||||||||
| dc.identifier.citation | Bone, 2011, v. 49 n. 6, p. 1290-1298 [How to Cite?] DOI: http://dx.doi.org/10.1016/j.bone.2011.08.031 | ||||||||
| dc.identifier.doi | http://dx.doi.org/10.1016/j.bone.2011.08.031 | ||||||||
| dc.identifier.epage | 1298 | ||||||||
| dc.identifier.hkuros | 207343 | ||||||||
| dc.identifier.isi | WOS:000297663500021
Funding Information: This study was supported by the Innovation and Technology Fund (ITF; Project ref. no. GHP/009/06), Hong Kong Research Grants Council (RGC) Grant 714908 and National Institutes of Health (R01 AR051376). | ||||||||
| dc.identifier.issn | 8756-3282 2011 Impact Factor: 4.023 2011 SCImago Journal Rankings: 0.326 | ||||||||
| dc.identifier.issue | 6 | ||||||||
| dc.identifier.pmid | 21925296 | ||||||||
| dc.identifier.scopus | eid_2-s2.0-81355127486 | ||||||||
| dc.identifier.spage | 1290 | ||||||||
| dc.identifier.uri | http://hdl.handle.net/10722/143128 | ||||||||
| dc.identifier.volume | 49 | ||||||||
| dc.language | eng | ||||||||
| dc.publisher | Elsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/bone | ||||||||
| dc.publisher.place | United States | ||||||||
| dc.relation.ispartof | Bone | ||||||||
| dc.relation.references | References in Scopus | ||||||||
| dc.subject.mesh | Anabolic Agents - pharmacology | ||||||||
| dc.subject.mesh | Osteoblasts - drug effects - metabolism - pathology | ||||||||
| dc.subject.mesh | Osteoclasts - drug effects - metabolism - pathology | ||||||||
| dc.subject.mesh | Osteoprotegerin - genetics - metabolism | ||||||||
| dc.subject.mesh | Strontium - pharmacology - therapeutic use | ||||||||
| dc.title | The cross-talk between osteoclasts and osteoblasts in response to strontium treatment: involvement of osteoprotegerin | ||||||||
| dc.type | Article |
Author Affiliations
- Jinan University, School of Medicine
- Columbia University in the City of New York
- The University of Hong Kong