Direct and indirect radiation effects on osteoclast formation in vitro.
An in vitro co-culture system was applied to study the direct and indirect effects of irradiation on osteoclast formation. Osteoclast precursor-free fetal mouse metatarsal bones were employed as osteoclast-forming inductor and periostea dissected from fetal calvaria as source of proliferating progenitor cells. Direct radiation effects on the formation of osteoclasts were assessed in co-cultures of irradiated periostea and non-irradiated bone rudiments. The results showed that the (blood-borne) periosteal progenitors were rather radiosensitive. A radiation 'survival' curve of osteoclast formation in relation to various doses could be constructed yielding a mean lethal dose (Do value) of 0.94 +/- 0.02 Gy and an extrapolation number of 1.67 +/- 0.01. Irradiation of the fetal long bones by low doses, effective for direct elimination of osteoclast progenitor cells, did not indirectly affect osteoclast development from the non-irradiated periosteal progenitor population. However, at relatively high radiation levels, though not lethal for the long bone rudiments, a significant inhibition of osteoclast formation became evident. The results indicate that radiation primarily affects osteoclast formation via a direct action on radiosensitive, proliferating progenitor cells. Injury to long bone models by relatively high radiation doses may also lead to severe disturbance of osteoclast formation kinetics.
D000135:Acid Phosphatase / Q000032:analysis; D000818:Animals; D001842:Bone and Bones / Q000196:embryology / Q000528:radiation effects; D002454:Cell Differentiation / Q000528:radiation effects; D002470:Cell Survival / Q000528:radiation effects; D002478:Cells, Cultured; D004307:Dose-Response Relationship, Radiation; D051379:Mice; D010010:Osteoclasts / Q000166:cytology / Q000528:radiation effects*; D013234:Stem Cells / Q000528:radiation effects; D013644:Tartrates / Q000494:pharmacology
D013644:Tartrates; D000135:Acid Phosphatase; C029768:tartaric acid