Interleukin 10 inhibits transforming growth factor-beta (TGF-beta) synthesis required for osteogenic commitment of mouse bone marrow cells.
Interleukin 10 (IL-10) suppressed TGF-beta synthesis in mouse bone marrow cultures. Coincidingly, IL-10 down-regulated the production of bone proteins including alkaline phosphatase (ALP), collagen and osteocalcin, and the formation of mineralized extracellular matrix. The mAb 1D11.16 which neutralizes TGF-beta 1 and TGF-beta 2, induced suppressive effects comparable to IL-10 when administered before the increase of cell proliferation in the culture. It appears that mainly TGF-beta 1 plays a role in this system since (a) TGF-beta 2 levels were undetectable in supernatants from osteogenic cultures, (b) no effect was observed when the anti-TGF-beta 2 neutralizing mAb 4C7.11 was added and (c) the suppressive effect of IL-10 could be reversed by adding exogenous TGF-beta 1. It is unlikely that TGF-beta 1 modulates osteogenic differentiation by changing the proliferative potential of marrow cells since 1D11.16 did not affect [3H]thymidine ([3H]TdR) incorporation or the number of fibroblast colony forming cells (CFU-F) which harbor the osteoprogenitor cell population. Furthermore, 1D11.16 did not alter [3H]TdR uptake by the cloned osteoprogenitor cell lines MN7 and MC3T3. Light and scanning electron microscopy showed that IL-10 and 1D11.16 induced comparable morphological changes in the marrow cultures. Control cultures contained flat adherent cells embedded in a mineralized matrix. In contrast, IL-10 and 1D11.16 treated cultures were characterized by round non-adherent cells and the absence of a mineralized matrix. In this study, the mechanism by which IL-10 suppresses the osteogenic differentiation of mouse bone marrow was identified as inhibition of TGF-beta 1 production which is essential for osteogenic commitment of bone marrow cells.
Van Vlasselaer
P
P
Department of Environment, Vlaamse Instelling voor Technologisch Onderzoek (V.I.T.O.), Mol, Belgium.
Borremans
B
B
van Gorp
U
U
Dasch
J R
JR
De Waal-Malefyt
R
R
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001853:Bone Marrow / Q000648:ultrastructure; D001854:Bone Marrow Cells; D002454:Cell Differentiation; D002455:Cell Division; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D015536:Down-Regulation; D005109:Extracellular Matrix / Q000378:metabolism; D016753:Interleukin-10 / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008854:Microscopy, Electron; D015675:Osteocalcin / Q000378:metabolism; D010012:Osteogenesis / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*
D016212:Transforming Growth Factor beta; D015675:Osteocalcin; D016753:Interleukin-10; D003094:Collagen; D000469:Alkaline Phosphatase