Parathyroid hormone (PTH) and PTH-like protein (PLP) stimulate interleukin-6 production by osteogenic cells: a possible role of interleukin-6 in osteoclastogenesis.
Osteogenic cells mediate PTH-stimulated osteoclastic bone resorption by a yet unidentified mechanism. We show that primairy rat osteoblast-like cells and the clonal osteogenic sarcoma cell line UMR-106 produce interleukin-6 (IL-6) and that bPTH(1-84) and synthetic hPLP(1-34) stimulate this production dose-dependently. With both peptides a close relation between IL-6 and cyclic-AMP production was found, though for PTH concentrations higher than 2.10(-8) M a clear dissociation was observed. Significant IL-6 activity was also detected in media of cultures of 17-day-old fetal mouse radii and metacarpals which was clearly stimulated by PTH. The source of IL-6 in these bone explants seems to be the osteogenic (cartilage) cells. Treatment of bone explants with IL-6 induced osteoclastic resorption which, however, depended on the bone resorption system used. This bone resorbing action of IL-6 is exerted probably through an effect on the formation of osteoclasts (osteoclastogenesis) rather than on the activation of already existing mature osteoclasts. We suggest that IL-6 produced by osteogenic cells may be a mediator in PTH-stimulated osteoclastic bone resorption.
Löwik
C W
CW
Department of Endocrinology, University Hospital Leiden, The Netherlands.
van der Pluijm
G
G
Bloys
H
H
Hoekman
K
K
Bijvoet
O L
OL
Aarden
L A
LA
Papapoulos
S E
SE
D000818:Animals; D001862:Bone Resorption / Q000187:drug effects; D001842:Bone and Bones / Q000378:metabolism; D000242:Cyclic AMP / Q000096:biosynthesis; D066298:In Vitro Techniques; D015850:Interleukin-6; D007378:Interleukins / Q000096:biosynthesis* / Q000494:pharmacology; D051379:Mice; D009363:Neoplasm Proteins / Q000494:pharmacology*; D010006:Osteoblasts / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000494:pharmacology*; D044162:Parathyroid Hormone-Related Protein; D051381:Rats; D011994:Recombinant Proteins
D015850:Interleukin-6; D007378:Interleukins; D009363:Neoplasm Proteins; D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D011994:Recombinant Proteins; D000242:Cyclic AMP