Involvement of dual signal transduction systems in the stimulation of osteoclast-like cell formation by parathyroid hormone and parathyroid hormone-related peptide.
The present study was performed to examine whether parathyroid hormone (PTH) and parathyroid hormone-related peptide (PTHrP) would stimulate osteoclast-like cell formation via soluble factor(s) released from osteoblasts and, if so, to characterize the involvement of PTH/PTHrP-responsive dual signal transduction systems [cAMP-dependent protein kinase (PKA) and calcium/protein kinase C(PKC)]. Osteoblasts-conditioned medium (CM) was obtained from rat osteoblastic osteosarcoma cells (UMR-106 cells), which had been cultured in serum free medium for 24 hrs after treatment with various kinds of reagents. The CM of osteoblasts treated with either 10(-7) M human(h) PTH-(1-34) or 10(-7)M hPTHrP-(1-34) equally stimulated osteoclast-like cell formation from hemopoietic blast cells derived from mouse spleen cells, although the CM treated with 10(-8) M 1,25dihydroxyvitamin D3 failed to affect it. The CM treated with both 10(-4) M dibutyryl-cAMP and a direct PKA activator, 10(-4)M Sp-cAMPS significantly increased osteoclast-like cell formation. The CM treated with a PKC activator, 10(-7)M phorbol 12-myristate 13-acetate (PMA) and calcium ionophores (10(-7)M A23187 and 10(-7)M ionomycin) also significantly enhanced osteoclast-like cell formation. The present study first indicated that osteoblast-mediated stimulation of osteoclast-like cell formation by PTH and PTHrP, and the participation of PTH/PTHrP-responsive dual signal transduction systems of osteoblasts in the stimulation of osteoclast-like cell formation by PTH and PTHrP.
Department of Medicine, Kobe University School of Medicine, Japan.
H
H
Kaji
T
T
Sugimoto
M
M
Kanatani
M
M
Fukase
K
K
Chihara
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D016895:Culture Media, Serum-Free; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D015759:Ionomycin / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D012516:Osteosarcoma; D010281:Parathyroid Hormone / Q000494:pharmacology*; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D011506:Proteins / Q000494:pharmacology*; D051381:Rats; D015290:Second Messenger Systems / Q000187:drug effects; D015398:Signal Transduction; D019379:Teriparatide; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D017077:Culture Media, Conditioned; D016895:Culture Media, Serum-Free; C470121:PTHLH protein, human; D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; D011506:Proteins; D019379:Teriparatide; D000001:Calcimycin; D015759:Ionomycin; D003994:Bucladesine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D011494:Protein Kinases; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate