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Inhibitory effects of the bone-derived growth factors osteoinductive factor and transforming growth factor-beta on
R O Oreffo1, L Bonewald, A Kukita
1Department of Medicine, University of Texas Health Science Center, San Antonio 78284-7877.
Abstract:
Demineralized bone matrix contains a number of growth factors for osteoblast-like cells. Two of these, the novel glycoprotein osteoinductive factor (OIF) and transforming growth factor-beta (TGF beta), act together to cause ectopic bone formation in vivo. Since OIF, like TGF beta, is likely released from bone when the matrix is resorbed, we examined the effects of homogeneous OIF and TGF beta on osteoclast function. Osteoclast function was tested in isolated avian osteoclasts and was measured in terms of tartrate-resistant acid phosphatase (TRAP) activity, oxygen-derived free radical production, and formation of characteristic resorption lacunae on slices of sperm whale dentine. OIF (50-100 ng/ml) inhibited the capacity of these osteoclasts to form lacunae whether assessed by the number of excavations per slice or by the total area resorbed. OIF (10-100 ng/ml) or TGF beta (10-20 ng/ml) caused a decrease in TRAP activity as well as a reduction in oxygen-derived free radical generation detected by nitroblue tetrazolium staining. TGF beta had no effect on the resorption capacity of isolated osteoclasts in concentrations that inhibited TRAP activity and nitroblue tetrazolium staining. These results suggest that growth regulatory factors, such as OIF and TGF beta, released during the resorption of bone may be endogenous inhibitors of continued osteoclastic activity. This cessation of osteoclast activity may be an essential preliminary step to the new bone formation that occurs at resorption sites during bone remodeling.
Insights
Osteoinductive factor (OIF) and transforming growth factor-beta (TGF-β) inhibit osteoclast activity, reducing bone resorption. This suggests these bone growth factors may regulate bone remodeling by pausing osteoclasts before new bone formation.
Area of Science:
- Bone Biology
- Cellular Signaling
- Biochemistry
Background:
- Demineralized bone matrix contains growth factors crucial for osteoblast activity.
- Osteoinductive factor (OIF) and transforming growth factor-beta (TGF-β) promote ectopic bone formation.
- These factors are released during bone resorption, suggesting a role in regulating osteoclasts.
Purpose of the Study:
- To investigate the effects of OIF and TGF-β on isolated avian osteoclast function.
- To determine if OIF and TGF-β inhibit osteoclast resorption, TRAP activity, free radical production, and lacunae formation.
Main Methods:
- Isolated avian osteoclasts were used to assess function.
- Measurements included tartrate-resistant acid phosphatase (TRAP) activity.
- Resorption was quantified by lacunae formation on dentine slices.
- Oxygen-derived free radical production was detected using nitroblue tetrazolium staining.
Main Results:
- OIF significantly inhibited osteoclast resorption (lacunae formation) at 50-100 ng/ml.
- Both OIF (10-100 ng/ml) and TGF-β (10-20 ng/ml) decreased TRAP activity and free radical generation.
- TGF-β did not affect osteoclast resorption capacity despite inhibiting TRAP and free radical production.
Conclusions:
- OIF and TGF-β, released during bone resorption, may act as endogenous inhibitors of osteoclast activity.
- This inhibition of osteoclasts could be a critical step preceding new bone formation during remodeling.
- Growth factors play a regulatory role in the bone remodeling cycle.