Activated platelets positively regulate RANKL-mediated osteoclast differentiation.
Platelets induce osteoclastogenesis in total bone marrow cultures where hematopoietic cells can interact with stromal cells. Whether or not activated platelets directly act on hematopoietic cells to promote their differentiation into osteoclasts remains unknown. Here we report that platelet releasates (PRS) increase osteoclastogenesis in stroma-depleted, macrophage colony-stimulating factor (M-CSF)-dependent bone marrow cells when cultured in the presence of receptor activator of NF-kappaB ligand (RANKL). The increased number of tartrate-resistant acid phosphatase-positive multinucleated cells (MNC) was paralleled by an enhanced transcription of osteoclast specific genes. Osteoclastogenesis was observed with hematopoietic cells previously depleted of B-cells or T-cells. Immunoprecipitation of transforming growth factor-beta (TGF-beta) decreased the osteoclastogenic capacity of the PRS. PRS enhanced phosphorylation of Smad-2, a downstream signaling mediator of TGF-beta. PRS increased phosphorylation of p38 and c-Jun NH(2)-terminal kinase (JNK), whereas only blocking of p38 but not JNK signaling suppressed osteoclastogenesis. These results suggest that activated platelets can enhance osteoclastogenesis by providing a source of TGF-beta and by activating osteoclastogenic signaling pathways.
Weicht
Barbara
B
Department of Oral Surgery, Medical University Vienna, Vienna, Austria.
Maitz
Philipp
P
Kandler
Barbara
B
Fischer
Michael B
MB
Watzek
Georg
G
Gruber
Reinhard
R
D000135:Acid Phosphatase / Q000378:metabolism; D000328:Adult; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D010010:Osteoclasts / Q000502:physiology*; D015539:Platelet Activation; D011233:Precipitin Tests; D053245:RANK Ligand / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D013917:Thrombin / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D015854:Up-Regulation
D053245:RANK Ligand; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D016173:Macrophage Colony-Stimulating Factor; D000135:Acid Phosphatase; D013917:Thrombin