Qiaoling Xu

Pulsed electromagnetic fields partially preserve bone mass, microarchitecture, and strength by promoting bone formation in hindlimb-suspended rats.

A large body of evidence indicates that pulsed electromagnetic fields (PEMF), as a safe and noninvasive method, could promote in vivo and in vitro osteogenesis. Thus far, the effects and underlying mechanisms of PEMF on disuse osteopenia and/or osteoporosis remain poorly understood. Herein, the efficiency of PEMF on osteoporotic bone microarchitecture, bone strength, and bone metabolism, together with its associated signaling pathway mechanism, was systematically investigated in hindlimb‐unloaded (HU) rats. Thirty young mature (3‐month‐old), male Sprague‐Dawley rats were equally assigned to control, HU, and HU + PEMF groups. The HU + PEMF group was subjected to daily 2‐hour PEMF exposure at 15 Hz, 2.4 mT. After 4 weeks, micro–computed tomography (µCT) results showed that PEMF ameliorated the deterioration of trabecular and cortical bone microarchitecture. Three‐point bending test showed that PEMF mitigated HU‐induced reduction in femoral mechanical properties, including maximum load, stiffness, and elastic modulus. Moreover, PEMF increased serum bone formation markers, including osteocalcin (OC) and N‐terminal propeptide of type 1 procollagen (P1NP); nevertheless, PEMF exerted minor inhibitory effects on bone resorption markers, including C‐terminal crosslinked telopeptides of type I collagen (CTX‐I) and tartrate‐resistant acid phosphatase 5b (TRAcP5b). Bone histomorphometric analysis demonstrated that PEMF increased mineral apposition rate, bone formation rate, and osteoblast numbers in cancellous bone, but PEMF caused no obvious changes on osteoclast numbers. Real‐time PCR showed that PEMF promoted tibial gene expressions of Wnt1, LRP5, β‐catenin, OPG, and OC, but did not alter RANKL, RANK, or Sost mRNA levels. Moreover, the inhibitory effects of PEMF on disuse‐induced osteopenia were further confirmed in 8‐month‐old mature adult HU rats. Together, these results demonstrate that PEMF alleviated disuse‐induced bone loss by promoting skeletal anabolic activities, and imply that PEMF might become a potential biophysical treatment modality for disuse osteoporosis.

Circadian rhythm affects the preventive role of pulsed electromagnetic fields on ovariectomy-induced osteoporosis in rats

Pulsed electromagnetic fields (PEMF) have been proved effective in the prevention of osteoporosis both experimentally and clinically. Chronotherapy studies have shown that circadian rhythm (CR) played an important role in the occurrence, development and treatment of several diseases. CR has also been recognized as an essential feature of bone metabolism. Therefore, it is of therapeutic significance to investigate the impact of CR on the efficacy of PEMF in the prevention of osteoporosis. However, this issue has never been discussed previously. The objective of this study was to systematically evaluate the impact of CR on the preventive effect of PEMF on osteoporosis in rats. Thirty-two 3 month old female Sprague-Dawley rats were randomly divided into four different groups: sham-operated control (Sham), ovariectomy (OVX), OVX with PEMF stimulation in daytime (OVX+DPEMF) and OVX with PEMF stimulation in nighttime (OVX+NPEMF) groups. The OVX+DPEMF and OVX+NPEMF groups were subjected to daily PEMF exposure on the 2nd post-operative day, from 9:00 to 15:00, and 0:00 to 6:00, respectively. After 12 weeks, the OVX+DPEMF group presented better efficacy in prevention against OVX-induced bone loss and deterioration of trabecular bone architecture compared with the OVX+NPEMF group. This was evidenced by the increased levels of femoral bone mineral density, trabecular area percentage, trabecular thickness, trabecular number and decreased trabecular separation. Furthermore, the bone turnover biomarkers (serum alkaline phosphatase, serum bone Gla protein and urinary deoxypyridinoline) and the dynamic histomorphometric parameters reflecting the trabecular osteoblast and osteoclast activity (bone formation rate with bone volume as referent, osteoclast number, etc.) in the OVX+DPEMF group decreased to a larger extent compared with the OVX+NPEMF group. In conclusion, the results indicated that CR was an important factor determining the preventive effect of PEMF on osteoporosis and PEMF exposure in the daytime presented better stimulus efficacy in rats. The findings might be helpful for the efficacious use of PEMF mediations, evaluation of PEMF action and experimental design in the future studies of biological effect of electromagnetic fields.

Prevalence and Predictors of Mild Cognitive Impairment in Xi’an: A Community-Based Study among the Elders

Mild cognitive impairment (MCI) is an intermediate stage between normal cognitive function and dementia among aging individuals. This study was designed to estimate the prevalence of MCI and explore the possible risk factors including gender disparities among community-dwelling older individuals. The study was conducted in Xi’an, China. This is a cross-sectional study. A total of 815 individuals, 60 years and older were selected by stratified random cluster sampling. Cognitive function was measured using the mini-mental status examination (MMSE), the Chinese version of the Dementia Rating Scales (CDRS) was used to apply the diagnostic of non-dementia, and activities of daily living (ADL) and instrumental activities of daily living (IADL) systems were used to functional status. The association between sociodemographic characteristics, lifestyle, history of chronic diseases and MCI were evaluated separately for men and women using the Pearson χ2- test and binary logistic regression. Of the 815 community-dwelling individuals, 145 were found to have MCI. Overall, the prevalence of MCI was 18.5%, with a prevalence of 19.6% in women (105/535), and 15.3% (40/261) in men. The results of the binary logistical regression analysis indicated that age and history of stroke were associated with MCI in men. For women, the risk factors were lower level of educational and lack of religious attendance. Results suggested that the factors capable of influencing MCI differed profoundly between older men and older women. For this reason, different preventative measures should be adopted to delay or reverse cognitive impairment among community-dwelling older men and women.

Effects of 180 mT static magnetic fields on diabetic wound healing in rats.

Diabetic wound (DW) problems are becoming a formidable clinical challenge due to the sharp increase in the diabetic population and the high incidence of DW. Static magnetic field (SMF) therapy, an inexpensive and accessible noninvasive method, has been proven to be effective on various tissue repairs. However, the issue of the therapeutic effect of SMF on DW healing has never been investigated. The objective of this study was to systematically evaluate the effect of a 180 mT moderate-intensity gradient SMF on DW healing in streptozotocin-induced diabetic rats. Forty-eight 3-month-old male Sprague-Dawley rats (32 diabetic and 16 non-diabetic rats) were assigned to three equal groups: normal wound, DW, and DW + SMF groups. An open circular wound with 1.5 cm diameter was created in the dorsum. The wound was covered with a dressing and the magnet was fixed on top of the dressing. On days 5, 12, and 19, four rats of each group were euthanized and gross wound area, histology and tensile strength were evaluated. The wound area determination suggested that SMF significantly increased the healing rate and reduced the gross healing time. This result was further confirmed by histological observations. The wound tensile strength, reflecting the amount and quality of collagen deposition, increased to a larger extent in the DW + SMF group on days 12 and 19 compared with the DW group. The results indicated that 180 mT SMF presented a beneficial effect on DW healing, and implied the clinical potential of SMF therapy in accelerating DW repair and releasing the psychological and physical burdens of diabetic patients.

Pulsed electromagnetic fields promote osteogenesis and osseointegration of porous titanium implants in bone defect repair through a Wnt/β-catenin signaling-associated mechanism

Treatment of osseous defects remains a formidable clinical challenge. Porous titanium alloys (pTi) have been emerging as ideal endosseous implants due to the excellent biocompatibility and structural properties, whereas inadequate osseointegration poses risks for unreliable long-term implant stability. Substantial evidence indicates that pulsed electromagnetic fields (PEMF), as a safe noninvasive method, inhibit osteopenia/osteoporosis experimentally and clinically. We herein investigated the efficiency and potential mechanisms of PEMF on osteogenesis and osseointegration of pTi in vitro and in vivo. We demonstrate that PEMF enhanced cellular attachment and proliferation, and induced well-organized cytoskeleton for in vitro osteoblasts seeded in pTi. PEMF promoted gene expressions in Runx2, OSX, COL-1 and Wnt/β-catenin signaling. PEMF-stimulated group exhibited higher Runx2, Wnt1, Lrp6 and β-catenin protein expressions. In vivo results via μCT and histomorphometry show that 6-week and 12-week PEMF promoted osteogenesis, bone ingrowth and bone formation rate of pTi in rabbit femoral bone defect. PEMF promoted femoral gene expressions of Runx2, BMP2, OCN and Wnt/β-catenin signaling. Together, we demonstrate that PEMF improve osteogenesis and osseointegration of pTi by promoting skeletal anabolic activities through a Wnt/β-catenin signaling-associated mechanism. PEMF might become a promising biophysical modality for enhancing the repair efficiency and quality of pTi in bone defect.

Pulsed electromagnetic fields promote in vitro osteoblastogenesis through a Wnt/β-catenin signaling-associated mechanism

Substantial evidence indicates that pulsed electromagnetic fields (PEMF) could accelerate fracture healing and enhance bone mass, whereas the unclear mechanism by which PEMF stimulation promotes osteogenesis limits its extensive clinical application. In the present study, effects and potential molecular signaling mechanisms of PEMF on in vitro osteoblasts were systematically investigated. Osteoblast-like MC3T3-E1 cells were exposed to PEMF burst (0.5, 1, 2, or 6 h/day) with 15.38 Hz at various intensities (5 Gs (0.5 mT), 10 Gs (1 mT), or 20 Gs (2 mT)) for 3 consecutive days. PEMF stimulation at 20 Gs (2 mT) for 2 h/day exhibited most prominent promotive effects on osteoblastic proliferation via Cell Counting kit-8 analyses. PEMF exposure induced well-organized cytoskeleton, and promoted formation of extracellular matrix mineralization nodules. Significantly increased proliferation-related gene expressions at the proliferation phase were observed after PEMF stimulation, including Ccnd 1 and Ccne 1. PEMF resulted in significantly increased gene and protein expressions of alkaline phosphatase and osteocalcin at the differentiation phase of osteoblasts rather than the proliferation phase via quantitative reverse transcription polymerase chain reaction and Western blotting analyses. Moreover, PEMF upregulated gene and protein expressions of collagen type 1, Runt-related transcription factor 2 and Wnt/β-catenin signaling (Wnt1, Lrp6, and β-catenin) at proliferation and differentiation phases. Together, our present findings highlight that PEMF stimulated osteoblastic functions through a Wnt/β-catenin signaling-associated mechanism and, hence, regulates downstream osteogenesis-associated gene/protein expressions. Bioelectromagnetics. 37:152-162, 2016.

Effect of low-level mechanical vibration on osteogenesis and osseointegration of porous titanium implants in the repair of long bone defects.

Emerging evidence substantiates the potential of porous titanium alloy (pTi) as an ideal bone-graft substitute because of its excellent biocompatibility and structural properties. However, it remains a major clinical concern for promoting high-efficiency and high-quality osseointegration of pTi, which is beneficial for securing long-term implant stability. Accumulating evidence demonstrates the capacity of low-amplitude whole-body vibration (WBV) in preventing osteopenia, whereas the effects and mechanisms of WBV on osteogenesis and osseointegration of pTi remain unclear. Our present study shows that WBV enhanced cellular attachment and proliferation, and induced well-organized cytoskeleton of primary osteoblasts in pTi. WBV upregulated osteogenesis-associated gene and protein expression in primary osteoblasts, including OCN, Runx2, Wnt3a, Lrp6 and β-catenin. In vivo findings demonstrate that 6-week and 12-week WBV stimulated osseointegration, bone ingrowth and bone formation rate of pTi in rabbit femoral bone defects via μCT, histological and histomorphometric analyses. WBV induced higher ALP, OCN, Runx2, BMP2, Wnt3a, Lrp6 and β-catenin, and lower Sost and RANKL/OPG gene expression in rabbit femora. Our findings demonstrate that WBV promotes osteogenesis and osseointegration of pTi via its anabolic effect and potential anti-catabolic activity, and imply the promising potential of WBV for enhancing the repair efficiency and quality of pTi in osseous defects.

Wavelet analysis of acute effects of static magnetic field on resting skin blood flow at the nail wall in young men

Whether static magnetic field (SMF) can affect microcirculation and microvasculature in human is still ambiguous. In this study, laser Doppler flowmetry (LDF) combined with spectral analysis by wavelet transform was applied to investigate acute SMF-related effects on resting skin blood flow (SBF) at the nail walls. 18 healthy young male volunteers were randomly categorized into two groups: (1) intervention group (INT; n=9) and (2) control group (CTL; n=9). In each group, three 30-minute intervals (pre-exposure, exposure and post-exposure intervals) of continuous LDF recording were taken to evaluate the baseline, SMF effects and its deferred effects. During the exposure interval in the INT group, a neodymium-iron-boron magnet was laid under the middle finger prominence while a sham was used in the CTL group. The effective flux density range of SMF along the axis of the magnet was about 46 to 223 mT between the sites of SBF measurement and the magnet. No intervention existed during other 30-minute intervals in either group. Thereafter, analysis of variance with repeated-measures combined with Bonferronis multiple comparison tests was adopted to analyze the SBF value and its spectral variants obtained by wavelet transform. The major finding of this study was that SMF exposure induced significant increases in the absolute amplitudes of frequency band III and V (aIII and aV), which indicated intrinsic myogenic and endothelial related activities (P<0.05) respectively while the mean amplitude of SBF flux still maintain on the basal level (P>0.05). Furthermore, after removal of the SMF, variations of rhythmic flow motion of SBF in SMF exposure interval vanished gradually, which suggest the limitations of the deferred-effect of SMF on SBF.

Therapeutic effects of 15 Hz pulsed electromagnetic field on diabetic peripheral neuropathy in streptozotocin-treated rats.

Although numerous clinical studies have reported that pulsed electromagnetic fields (PEMF) have a neuroprotective role in patients with diabetic peripheral neuropathy (DPN), the application of PEMF for clinic is still controversial. The present study was designed to investigate whether PEMF has therapeutic potential in relieving peripheral neuropathic symptoms in streptozotocin (STZ)-induced diabetic rats. Adult male Sprague–Dawley rats were randomly divided into three weight-matched groups (eight in each group): the non-diabetic control group (Control), diabetes mellitus with 15 Hz PEMF exposure group (DM+PEMF) which were subjected to daily 8-h PEMF exposure for 7 weeks and diabetes mellitus with sham PEMF exposure group (DM). Signs and symptoms of DPN in STZ-treated rats were investigated by using behavioral assays. Meanwhile, ultrastructural examination and immunohistochemical study for vascular endothelial growth factor (VEGF) of sciatic nerve were also performed. During a 7-week experimental observation, we found that PEMF stimulation did not alter hyperglycemia and weight loss in STZ-treated rats with DPN. However, PEMF stimulation attenuated the development of the abnormalities observed in STZ-treated rats with DPN, which were demonstrated by increased hind paw withdrawal threshold to mechanical and thermal stimuli, slighter demyelination and axon enlargement and less VEGF immunostaining of sciatic nerve compared to those of the DM group. The current study demonstrates that treatment with PEMF might prevent the development of abnormalities observed in animal models for DPN. It is suggested that PEMF might have direct corrective effects on injured nerves and would be a potentially promising non-invasive therapeutic tool for the treatment of DPN.

Pulsed electromagnetic fields (PEMF) attenuate changes in vertebral bone mass, architecture and strength in ovariectomized mice

Pulsed electromagnetic fields (PEMF) has been investigated as a noninvasive alternative method to prevent bone loss for postmenopausal osteoporosis (OP), and the bone tissue involved in these studies are usually long bones such as femur and tibia in OP patients or rat models. However, few studies have investigated the effects of PEMF on the vertebral bone in mice with OP. This study aimed to investigate whether PEMF preserve lumbar vertebral bone mass, microarchitecture and strength in ovariectomized (OVX) mouse model of OP and its associated mechanisms. Thirty 3-month-old female BALB/c mice were randomly divided into three groups (n=10): sham-operated control (Sham), ovariectomy (OVX), and ovariectomy with PEMF treatment (OVX+PEMF). The OVX+PEMF group was exposed to 15Hz, 1.6 mT PEMF for 8h/day, 7days/week. After 8weeks, the mice were sacrificed. The OVX+PEMF group showed lower body weight gain of mice induced by estrogen deficiency compared with OVX group. Biochemical analysis of serum demonstrated that serum bone formation markers including bone specific alkaline phosphatase (BALP), serum osteocalcin (OCN), osteoprotegerin (OPG) and N-terminal propeptide of type I procollagen (P1NP) were markedly higher in OVX+PEMF group compared with OVX group. Besides, serum bone resorption markers including tartrate-resistant acid phosphatase 5b (TRAP-5b) and C-terminal crosslinked telopeptides of type I collagen (CTX-I) were markedly lower in OVX+PEMF group compared with OVX group. Biomechanical test observed that OVX+PEMF group showed higher compressive maximum load and stiffness of the lumbar vertebrae compared with OVX group. Micro-computed tomography (μCT) and histological analysis of lumbar vertebrae revealed that PEMF partially prevented OVX-induced decrease of trabecular bone mass and deterioration of trabecular bone microarchitecture in lumbar vertebrae. Real-time PCR showed that the canonical Wnt signaling pathway of the lumbar vertebrae, including Wnt3a, LRP5 and β-catenin were markedly up-regulated in OVX+PEMF group compared with OVX group. Moreover, the mRNA expressions of RANKL and OPG were markedly up-regulated in OVX+PEMF group compared with OVX group, whereas no statistical difference in RANKL/OPG mRNA ratio was found between OVX+PEMF group and OVX group. Besides, our study also found that the RANK mRNA expression was down-regulated in OVX+PEMF group compared with OVX group. Taken together, we reported that long-term stimulation with PEMF treatment was able to alleviate lumbar vertebral OP in postmenopausal mice through a combination of increased bone formation and suppressed bone resorption related to regulating the skeletal gene expressions of Wnt3a/LRP5/β-catenin and OPG/RANKL/RANK signaling pathways.