Osteoclast formation together with interleukin-6 production in mouse long bones is increased by insulin-like growth factor-I.
Insulin-like growth factor-I (IGF-I) is a potent stimulator of bone formation. Whether this growth factor also induces bone resorption has not been studied in detail. We used two organ culture systems to examine the direct effect of IGF-I on bone resorption. Fetal mouse radii/ulnae, containing mature osteoclasts, showed no response to IGF-I, indicating that osteoclastic activity is not influenced by IGF-I. Fetal mouse metacarpals/metatarsals, containing just osteoclast precursors and progenitors, showed an increase in resorption in response to IGF-I, indicating that IGF-I stimulates the formulation of osteoclast precursors/progenitors and thereby increases the number of osteoclasts. Interleukin-6 (IL-6) has been hypothesized to be a mediator of bone resorptive agents such as parathyroid hormone (PTH). Both radii/ulnae and metacarpals/metatarsals reacted to IGF-I with an increase in IL-6 production. IL-6 production by UMR-106 osteogenic osteosarcoma cells was positively modulated by IGF-I, indicating that osteoblasts are likely to be the cells responsible for increased IL-6 production by the bones, and that IL-6 might be a mediatory of IGF-I-stimulated bone resorption.
Slootweg
M C
MC
Scientific Development Group, Organon International bv, Oss, The Netherlands.
Most
W W
WW
van Beek
E
E
Schot
L P
LP
Papapoulos
S E
SE
Löwik
C W
CW
D000818:Animals; D001862:Bone Resorption / Q000503:physiopathology*; D001842:Bone and Bones / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D015850:Interleukin-6 / Q000096:biosynthesis*; D051379:Mice; D008815:Mice, Inbred Strains; D009924:Organ Culture Techniques; D010010:Osteoclasts / Q000502:physiology*; D010281:Parathyroid Hormone / Q000502:physiology
D015850:Interleukin-6; D010281:Parathyroid Hormone; D007334:Insulin-Like Growth Factor I