Pulsed Electromagnetic Fields Improve Bone Microstructure and Strength in Ovariectomized Rats through a Wnt/Lrp5/β-Catenin Signaling-Associated Mechanism

Abstract

Growing evidence has demonstrated that pulsed electromagnetic field (PEMF), as an alternative noninvasive method, could promote remarkable in vivo and in vitro osteogenesis. However, the exact mechanism of PEMF on osteopenia/osteoporosis is still poorly understood, which further limits the extensive clinical application of PEMF. In the present study, the efficiency of PEMF on osteoporotic bone microarchitecture and bone quality together with its associated signaling pathway mechanisms was systematically investigated in ovariectomized (OVX) rats. Thirty rats were equally assigned to the Control, OVX and OVX+PEMF groups. The OVX+PEMF group was subjected to daily 8-hour PEMF exposure with 15 Hz, 2.4 mT (peak value). After 10 weeks, the OVX+PEMF group exhibited significantly improved bone mass and bone architecture, evidenced by increased BMD, Tb.N, Tb.Th and BV/TV, and suppressed Tb.Sp and SMI levels in the MicroCT analysis. Three-point bending test suggests that PEMF attenuated the biomechanical strength deterioration of the OVX rat femora, evidenced by increased maximum load and elastic modulus. RT-PCR analysis demonstrated that PEMF exposure significantly promoted the overall gene expressions of Wnt1, LRP5 and β-catenin in the canonical Wnt signaling, but did not exhibit obvious impact on either RANKL or RANK gene expressions. Together, our present findings highlight that PEMF attenuated OVX-induced deterioration of bone microarchitecture and strength in rats by promoting the activation of Wnt/LRP5/β-catenin signaling rather than by inhibiting RANKL-RANK signaling. This study enriches our basic knowledge to the osteogenetic activity of PEMF, and may lead to more efficient and scientific clinical application of PEMF in inhibiting osteopenia/osteoporosis.

Pulsed electromagnetic fields stimulate osteogenic differentiation and maturation of osteoblasts by upregulating the expression of BMPRII localized at the base of primary cilium

“…As some treatments are defective, ineffective, expensive, low in patient compliance, and/or risky (as they disturb normal bone turnover physiology and/or cause significant side effects or even cancer), searching for alternative and effective therapies for osteoporosis is necessary and has been drawing attention of many clinicians and researchers [1,2]. While electromagnetic fields (EMFs) of extremely low frequency have been considered as a promising therapy for a wide range of bone diseases, such as fresh and nonunion fractures and osteoarthritis [3], accumulating evidence has now shown that pulsed electromagnetic fields (PEMFs) as an alternative noninvasive method were capable of producing satisfying therapeutic effects on osteoporosis [4]. PEMFs promote osteogenesis and mineralization of bone cells and prevent bone loss in animal models of disuse or tail-suspension osteoporosis and ovariectomy-induced bone loss [5,6].…”

Pulsed electromagnetic fields inhibit bone loss in streptozotocin-induced diabetic rats

“…Many studies have shown the favorable effects of PEMFs on osteoporosis in OVX or hindlimb-suspended animals [6][7][8][9]. However, few studies have evaluated the effects of PEMFs on bone mass, bone microarchitecture, and bone strength together with their related signaling pathway mechanisms in animal models of diabetic osteopenia.…”

“…As a safe and noninvasive physiotherapy, pulsed electromagnetic fields (PEMFs) have been suggested as a promising treatment for diabetic osteopenia. It has been reported that PEMFs can increase bone mineral density (BMD) in osteoporosis patients [5], prevent bone loss in ovariectomy-induced osteoporosis rats [6][7][8] and hindlimb-suspended rats [9], improve bone formation [10,11], and inhibit bone resorption [12] in vitro. It has reported that the cellular functions of bone marrow stromal cell [13], osteoblast [14,15], and osteoclast [16,17] are abnormal under diabetic conditions.…”

“…In vitro study has reported that PEMFs were capable of increasing the cellular differentiation in MC3T3-E1 osteoblasts [23]. In vivo studies have shown that [7,8] PEMFs inhibited OVXinduced bone loss and deterioration of bone microarchitecture and strength in rats by promoting the activation of Wnt/b-catenin signaling.…”

Underlying Signaling Pathways and Therapeutic Applications of Pulsed Electromagnetic Fields in Bone Repair

“…Furthermore, the enhanced Wnt/β-catenin signaling induced by PEMFs notably elevated the expression of proliferation phase related target genes, Ccnd 1 and Ccne 1, and differentiation phase related genes, ALP, OCN, COL1, and Runx2, in osteoblast cells, which accelerated the osteoblasts proliferation, differentiation, and mineralization, three pivotal processes of bone formation [31, 32]. On the other hand, according to in vivo assay studies, PEMFs effectively reversed the bone mass loss and deterioration of bone microarchitecture analyzed by microCT and attenuated biomechanical strength deterioration evaluated by three-point bending test in hind limb-suspended ovariectomized rats through the Wnt/Lrp5/β-catenin signal pathway [33, 34], indicating that activating this pathway by PEMF exposure is beneficial for bone disorders.…”