Platelet-released supernatants stimulate formation of osteoclast-like cells through a prostaglandin/RANKL-dependent mechanism

Platelets are activated at fracture sites or upon the insertion of implants as a consequence of vascular disruption and secrete the contents of their granules into the developing hematoma. The regeneration of injured tissue requires bone remodeling and the resorbing activity of osteoclasts. To test...

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Veröffentlicht in:Bone (New York, N.Y.) N.Y.), 2002-05, Vol.30 (5), p.726-732
Hauptverfasser: Gruber, R, Karreth, F, Fischer, M.B, Watzek, G
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creator Gruber, R
Karreth, F
Fischer, M.B
Watzek, G
description Platelets are activated at fracture sites or upon the insertion of implants as a consequence of vascular disruption and secrete the contents of their granules into the developing hematoma. The regeneration of injured tissue requires bone remodeling and the resorbing activity of osteoclasts. To test our hypothesis that platelets can stimulate osteoclastogenesis, we examined the effects of supernatants released from thrombin-activated platelets on osteoclast-like cell formation in murine bone marrow cultures. Histochemical analysis indicated the presence of bone-resorbing, tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells. Transcripts that are characteristically expressed in native osteoclasts were increased in these cultures, as determined by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis. The inhibition of both cyclooxygenases with indomethacin, as well as the addition of the cyclooxygenase-2 (COX-2)-selective antagonist, NS398, completely blocked osteoclast-like cell formation and decreased endogenous prostaglandin E 2 production. Platelet-released supernatants stimulated the expression of receptor activator of NF-κB ligand (RANKL), whereas mRNA levels of osteoprotegerin (OPG) were decreased. The formation of osteoclast-like cells was prevented by recombinant OPG. Our results suggest that COX-2 activity is necessary for osteoclast-like cell formation in response to platelet-released supernatants, and that endogenously produced prostaglandin E 2 can, in turn, increase the RANKL:OPG ratio, indicating that platelets can contribute to bone remodeling by stimulation of osteoclastogenesis.
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Platelet-released supernatants stimulated the expression of receptor activator of NF-κB ligand (RANKL), whereas mRNA levels of osteoprotegerin (OPG) were decreased. The formation of osteoclast-like cells was prevented by recombinant OPG. 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The regeneration of injured tissue requires bone remodeling and the resorbing activity of osteoclasts. To test our hypothesis that platelets can stimulate osteoclastogenesis, we examined the effects of supernatants released from thrombin-activated platelets on osteoclast-like cell formation in murine bone marrow cultures. Histochemical analysis indicated the presence of bone-resorbing, tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells. Transcripts that are characteristically expressed in native osteoclasts were increased in these cultures, as determined by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis. The inhibition of both cyclooxygenases with indomethacin, as well as the addition of the cyclooxygenase-2 (COX-2)-selective antagonist, NS398, completely blocked osteoclast-like cell formation and decreased endogenous prostaglandin E 2 production. Platelet-released supernatants stimulated the expression of receptor activator of NF-κB ligand (RANKL), whereas mRNA levels of osteoprotegerin (OPG) were decreased. The formation of osteoclast-like cells was prevented by recombinant OPG. Our results suggest that COX-2 activity is necessary for osteoclast-like cell formation in response to platelet-released supernatants, and that endogenously produced prostaglandin E 2 can, in turn, increase the RANKL:OPG ratio, indicating that platelets can contribute to bone remodeling by stimulation of osteoclastogenesis.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Blood Platelets - metabolism</subject><subject>Bone marrow culture</subject><subject>Carrier Proteins - genetics</subject><subject>Carrier Proteins - metabolism</subject><subject>Cell Differentiation - drug effects</subject><subject>Cell Differentiation - physiology</subject><subject>Cells, Cultured</subject><subject>Cyclooxygenase 1</subject><subject>Cyclooxygenase 2</subject><subject>Cyclooxygenase-2 (COX-2)</subject><subject>Dinoprostone - metabolism</subject><subject>Fundamental and applied biological sciences. 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The regeneration of injured tissue requires bone remodeling and the resorbing activity of osteoclasts. To test our hypothesis that platelets can stimulate osteoclastogenesis, we examined the effects of supernatants released from thrombin-activated platelets on osteoclast-like cell formation in murine bone marrow cultures. Histochemical analysis indicated the presence of bone-resorbing, tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells. Transcripts that are characteristically expressed in native osteoclasts were increased in these cultures, as determined by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis. The inhibition of both cyclooxygenases with indomethacin, as well as the addition of the cyclooxygenase-2 (COX-2)-selective antagonist, NS398, completely blocked osteoclast-like cell formation and decreased endogenous prostaglandin E 2 production. Platelet-released supernatants stimulated the expression of receptor activator of NF-κB ligand (RANKL), whereas mRNA levels of osteoprotegerin (OPG) were decreased. The formation of osteoclast-like cells was prevented by recombinant OPG. Our results suggest that COX-2 activity is necessary for osteoclast-like cell formation in response to platelet-released supernatants, and that endogenously produced prostaglandin E 2 can, in turn, increase the RANKL:OPG ratio, indicating that platelets can contribute to bone remodeling by stimulation of osteoclastogenesis.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>11996911</pmid><doi>10.1016/S8756-3282(02)00697-X</doi><tpages>7</tpages></addata></record>
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source MEDLINE; Access via ScienceDirect (Elsevier)
subjects Animals
Biological and medical sciences
Blood Platelets - metabolism
Bone marrow culture
Carrier Proteins - genetics
Carrier Proteins - metabolism
Cell Differentiation - drug effects
Cell Differentiation - physiology
Cells, Cultured
Cyclooxygenase 1
Cyclooxygenase 2
Cyclooxygenase-2 (COX-2)
Dinoprostone - metabolism
Fundamental and applied biological sciences. Psychology
Gene Expression - physiology
Glycoproteins - genetics
Glycoproteins - metabolism
Glycoproteins - pharmacology
Isoenzymes - antagonists & inhibitors
Isoenzymes - metabolism
Membrane Glycoproteins - genetics
Membrane Glycoproteins - metabolism
Membrane Proteins
Mice
Mice, Inbred Strains
NF-kappa B - metabolism
Osteoclast
Osteoclasts - cytology
Osteoclasts - metabolism
Osteoprotegerin
Platelet-rich plasma
Platelets
Prostaglandin-Endoperoxide Synthases - metabolism
RANK Ligand
receptor activator of NF-κB ligand (RANKL)
Receptor Activator of Nuclear Factor-kappa B
Receptors, Cytoplasmic and Nuclear - genetics
Receptors, Cytoplasmic and Nuclear - metabolism
Receptors, Tumor Necrosis Factor
Recombinant Proteins - pharmacology
RNA, Messenger - analysis
Skeleton and joints
Vertebrates: osteoarticular system, musculoskeletal system
title Platelet-released supernatants stimulate formation of osteoclast-like cells through a prostaglandin/RANKL-dependent mechanism
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