The Role Of Classical Wnt Signaling Pathway In The Treatment Of Osteoporotic Fractures With Pulsed Electromagnetic Fields

With the increasing morbidity and associated healthcare burdens,fracture in osteoporotic bones has become a top health issue.The treatment of fracture healing in osteoporotic bones has been one of the major goals of modern orthopedic surgeons.Pulsed electromagnetic field(PEMF)providing noninvasive and systemic mechanical stimuli,has been proven osteogenic for intact bone and beneficial for fracture healing,which implies a potential of biophysical enhancement for fracture healing in osteoporotic bones.By animal experiment,we verify PEMF benefited the treatment of osteoporosic fracture healing and research the role of Wnt/?-catenin pathway.Objective:This study addressed the question of how PEMF affect fracture healing in osteoporotic bones through testifying the following hypotheses in a rat model:1)PEMF would benefit fracture healing in osteoporotic bones by providing a noninvasive biophysical stimulation;2)PEMF would promote callus formation,mineralization and remodeling during a secondary fracture healing process;3)PEMF would stimulate Wnt/?-catenin pathway related cellular activities and molecular events,and hence benefit fracture healing in osteoporotic bones.Method:Osteoporotic model was established in fifty-two 9-month-oldfemale SD rats following 3 months of inducement after ovariectomy.Closed femoralfracture was then created.Rats were randomized into vibration treatment group(EG)or sham-treated control(CG).Fracture healing status was monitored weekly by A-P and lateral radiographies and external callus width(CW)and callusarea(CA)were measured on the digitized lateral view images during the study period.The specimens were stained withHematoxylin-Eosin(H&E)and safranin-O/fast green(Saf-O)and the total callus area(Cl.Ar)and the cartilage area(Cg.Ar)were measured,and the percentage of the cartilage area to the total callus area was calculated as Cg.Ar/Cl.Ar.We verify PEMF has a role for the treatment ofracture healing in osteoporotic bones.Various genes of Wnt/?-catenin signaling were analyzed by quantitative real-time PCR.Result:Larger amount of callus(P=0.016 in radiograph)and more activechondrogenesis(P= 0.011)were observed in the EG group during the first 3 weeks sincethe start of the treatment.Afterwards,faster endochondral ossification and callusmineralization were observed,which resulted in a 33.3%higher rate in the EG group after 7 weeks of treatment.Quantitative RT-PCR revealed PEMF could increase Mrna levels of Wnt5a and?-catenin at special time point(P<0.05).Conclusion:The present study depicted the effects of PEMF on fracture healingin normal and osteoporotic rats.Key processes including chondrogenesis,endochondral ossification,and remodelling were all promoted by PEMF,which ledto faster callus formation,mineralization,remodeling and better mechanicaloutcomes.PEMF could benefit the fracture healing in osteoporotic bones via Wnt/?-catenin pathway.This study has provided solid basis for further clinical trials to confirm theefficacy of PEMF on fracture healing in patients.