Programmed cell death in post-traumatic bone callus

Some osteoblasts in the expanded population of periosteal cells that occurs following bone injury are removed from the callus by apoptosis, Our object ive was to study whether the consequences of activation of the death progra m could include feedback control of the healing response. Transforming grow th factor beta and interleukin-1 beta were delivered together continuously to a standardized tibial defect in rats for 3 days using implanted micro-os motic pumps. The bones were recovered at 1, 2, 3, 5, 7, 10 and 14 days afte r injury (n=6 in each treated and control group) and concentrations of prol iferating cells, osteoblasts and apoptotic bodies were determined. The inju ry-induced apoptotic component of the healing response was shifted in time due to the combined cytokines, compared with vehicle only, with the result that the peak in the concentration of apoptotic bodies occurred 2-3 days ea rlier in the treated animals. Neither osteoprogenitor proliferation nor ost eoblast concentration was affected by addition of the cytokines. The result s suggested that activation of apoptosis during injury repair was not neces sarily a passive consequence of the cellular response to injury. Programmed cell death could therefore have an active role in modulating bone repair.