Protective Effect Of PTH Against Hematopoietic Damage In Mice

The classic bone effect of Parathyroid hormone(PTH)is stimulating bone absorption. It has recently become very popular because they can treat osteoporosis by strongly stimulating bone formation and strengthening bone microarchitecture. It has been shown that PTH can strongly stimulate trabecular bone growth with bursts of adenyl cyclase activity and cyclic AMP production by activating PTH receptors on bone-lining cells and osteoblasts. Since, the size of the hematopoietic stem cells pool depends on the available trabecular bone niche space, the osteogenic PTH should increase the hematopoietic stem cells pool size and with this the effectiveness of the response to bone marrow injury.Objective: To investigate the protective effect of PTH on Cyclophosphamide or Radiation induced Hematopoietic Damage in mice.Methods:1. The KM mice were randomly divided into 3 groups :PTH group and normal group,control group .The mouse was administered with PTH[80μg/(kg ?d)] by intraperitoneal injection once a day in PTH group, equal distilled water was given to each mouse in control group by the same way ,nothing was done to the normal group After 4 days, these mice were whole body irradiated with 7.5 Gy 60Coγ-ray, then consecutively intraperitoneal injection for 14 days to found the differences among the PTH group , the control group and the normal group on weight,average survival time, mortal rate WBC,RBC and PLT, and histology were also performed in tibia. (2) C57BL/6J mice were exposed to sublethal doses of irradiation and human PTH(1-34) [80μg/(kg?d)]was subsequently injected intraperitoneally once daily for four weeks in these mice. Whole blood was collected from the tails of mice on sequential days(0d,5d,10d,15d,20d,30d) following irradiation and the blood cell numbers were determined by a hematocyte counter. Bone marrow progenitors were studied by determining colony forming units. (3) Cyclophosphamide (Cy)[250mg/(kg?d)] was administered to BALB/c mice for 3 days to establish bone marrow damage model. PTH group were administered with PTH[80μg/(kg?d)] by intraperitoneal injection after CY administration for 18days.Control group was administered with equal distilled water after CY administration to found the difference between the body weight and the survival time between two groups.Result :(1) PTH have markedly raised (p<0.05) the mice body weight that depressed by irradiation and prolonged the average survival time(p<0.05),improved the survival rate. In addition, the WBC, RBC and PLT in PTH group respectively regain to 50%, 78%,and 58%of normal group. (2) PTH treatment facilitated the recovery of circulating blood cell counts following radiation exposure. PTH-treated mice also demonstrated accelerated bone marrow cellular recovery, radioprotection of bone marrow progenitors and enhanced stem cell survival following irradiation compared with controls.(3)Bone marrow was damaged severely after CY administration. Mice died gradually in both groups. However, there have no significant differences between two groups (p>0.05).Conclusion: These observations suggest that PTH has the capability of reducing the damage of hematopoietic system in irradiated mice and has significant protective effect on mice against radiation injury. The protective role of PTH on CY-induced bone marrow damage needs more investigation.