Function Of A Specific Vessel Subtype In Osteoporosis And Its Clinical Significance

Investigation on the etiology of postmenopausal osteoporosis(type I)has been a difficult problem and a hot topic in the field of bone metabolism.Couple of osteogenesis and angiogenesis is a new research direction raised in recent years based on a specific vessel subtype(type H vessel)discovered in certain areas of bone.More important,type H vessels found in bone play pivotal roles in maintaining an appropriate metabolic niche for both the growth of blood vessels and bone formation where abundant osteoprogenitor cells are also noticed.Type H vessels mediate growth of bone vasculature,generate distinct metabolic and molecular microenvironments,maintain perivascular osteoporgenitors and couple angiogenesis to osteogenesis.Type H vessels show age-dependent decrease and its connection with osteoprogenitor cells is also impaired in elder mice.The pharmacological reversal of this decline allowed the restoration of bone mass.However,whether type H vessel has its function in decreased bone mineral density related diseases,especially in type I osteoporosis has not been reported.Further investigation on the correlation of type H vessels and bone formation is of great significance for the clinical treatment and prevention of osteoporosis.ObjectiveInvestigate the presence of type H vessel in human bone and its correlation with age and bone mineral density.Establish osteoporosis model and different ages mouse model to further verify the results found in human bone.Evaluate the feasibility of improving bone mineral density by enhancing the type H vessels formation.Methods1)Collect human bone samples from hip fracture patients,investigate whether the type H vessels were found in human bone by immunostaining and further analyze its correlation with age and bone mineral density.2)Establish two kinds of mouse models,including different weeks old mice(Young,Medium and Old)and postmenopausal osteoporosis mouse models by ovariectomy.Confirm the correlation between type H vessel and age.Further analyze the relationship between bone mineral density and type H vessel by micro-CT scanning and immunostaining.3)Freshly prepared desferrioxamine(DFO)was injected intraperitoneally every other day for 4 weeks in postmenopausal osteoporosis mouse models by ovariectomy.The samples were collected to evaluate the feasibility of improving bone mineral density by pharmaceutical vascular treatment.Results1)Confirmed the presence of type H vessels in human bone samples for the first time.Human type H vessels also show age-dependent decrease.Type H vessels in human bone decreased when low bone mineral density in the same age,which suggests a strong correlation between bone mineral density and type H vessels.2)Use different weeks old mice models confirm the type H vessels decreases with age.Synergistic decrease of bone mineral density and type H vessels were confirmed in ovariectomized mouse models.Use mouse model to verify the results found in human bone.3)Ovariectomized mouse models were made successfully.The mouse models were intraperitoneally injected with different doses of DFO.The results showed that administration of high dose DFO improved the bone quality along with increased type H vessel formation.Conclusions1)The presence of type H vessels in human bone was confirmed and its correlations with age and bone mineral density were also noticed.2)Correlation of type H vessel with bone mineral density and age were further verified in osteoporotic mouse models and different weeks old mouse models.3)Administration of high dose DFO can improve bone mineral density by enhancing type H vessels in ovariectomized mouse models.