Neuropeptide substance P stimulates the formation of osteoclasts via synovial fibroblastic cells.
The present study was designed to evaluate the effects of neuropeptide substance P (SP) on the formation of osteoclasts via synovial fibroblastic cells. Synovial fibroblastic cells derived from rat knee joint expressed the SP receptor, neurokinin-1 receptor (NK(1)-R). The addition of SP stimulated the proliferation of synovial fibroblastic cells and this effect was inhibited by SP or NK(1)-R antagonists. Increased expression of the receptor activator of nuclear factor kappaB ligand (RANKL) in synovial fibroblastic cells after the addition of SP was demonstrated by reverse transcriptase-polymerase chain reaction and immunofluorescence staining. Osteoprotegerin expression in synovial fibroblastic cells was decreased after incubation with SP. In co-cultures of synovial fibroblastic cells and rat peripheral blood monocytes, SP stimulated osteoclastogenesis. These results suggest that SP in the joint cavity may cause both hypertrophy of the synovium and induction of increased osteoclast formation through the increased expression of RANKL in the synovium.
Matayoshi
Takaaki
T
Division of Oral and Maxillofacial Reconstructive Surgery, Kyushu Dental College, Kitakyushu 803-8580, Japan.
Goto
Tetsuya
T
Fukuhara
Eiji
E
Takano
Hiroshi
H
Kobayashi
Shigeru
S
Takahashi
Tetsu
T
D000818:Animals; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000187:drug effects* / Q000502:physiology; D006023:Glycoproteins / Q000378:metabolism; D007150:Immunohistochemistry; D008024:Ligands; D016328:NF-kappa B / Q000378:metabolism; D009479:Neuropeptides / Q000494:pharmacology*; D010010:Osteoclasts / Q000187:drug effects* / Q000502:physiology; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics; D053244:Osteoprotegerin; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013373:Substance P / Q000494:pharmacology*; D013582:Synovial Fluid / Q000166:cytology
D006023:Glycoproteins; D008024:Ligands; D016328:NF-kappa B; D009479:Neuropeptides; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear; D018040:Receptors, Neurokinin-1; D018124:Receptors, Tumor Necrosis Factor; C506032:Tnfrsf11b protein, rat; D013373:Substance P