No abstract

Background Acupuncture at Zusanli (ST36) is often used to facilitate motor recovery after stroke. However, the effect of acupuncture at ST36 on motor cortical excitation and inhibition remains unclear. This study aimed to explore the effect of acupuncture at ST36 on motor cortical excitation and inhibition. Methods Twenty healthy volunteers were recruited to receive acupuncture treatment. We selected the acupoint ST36 and its respective sham point as the experimental acupoint. Transcranial magnetic stimulation (TMS) was used to measure motor‐evoked potentials (MEP) at 7 time points—before acupuncture (Pre), acupuncture (T0), 4 and 8 min after acupuncture (T4; T8), needle removal (T12), 4 and 8 min after needle removal (T16; T20). Simultaneously, paired TMS (pTMS) was employed to measure short‐ and long‐interval intracortical inhibition (SICI [short latency intracortical inhibition]; LICI [long latency intracortical inhibition]), respectively, at three time points—before acupuncture (Pre), acupuncture (T0), needle removal (T12). After removing the acupuncture needle, all subjects were asked to quantify their Deqi sensation using a Gas table. Results The average Deqi sensation score of all subjects during acupuncture at ST36 was higher than that observed at the sham point. With acupuncture at ST36, the MEP amplitude was higher at three time points (T0, T4, T8) than at Pre, although the MEP amplitude tended toward Pre after needle removal. The MEP amplitude was also higher at the same time points (T0, T4, T8) than at the sham point. Furthermore, the Deqi sensation score was correlated with MEP amplitude. With acupuncture at ST36, SICI and LICI at T0 were higher than those at Pre, and SICI and LICI at T0 were higher than those at the sham point. Conclusion Acupuncture at ST36 increased motor cortical excitation and had an effect on the remaining needle phase. Deqi sensation was correlated with MEP amplitude. Acupuncture at ST36 also decreased motor cortical inhibition.

It is widely accepted that mechanical stress is an important factor in bone associated cell differentiation, including that of mesenchymal stem cells, osteoblasts and osteocytes. The present study aimed to determine the effect of mechanical cyclic compressive load on osteoblast differentiation, and whether this was associated with activation of the wingless‑type (Wnt)/β-catenin signaling pathway. Using a 3D scaffold model, MC3T3‑E1 cells were exposed to cyclic compressive loading via the Flexcell‑5000C™ Compression system. Sinusoidal wave magnitudes of 0.33, 0.5 and 1 MPa were applied for 4, 6 and 8 h, at 1 Hz frequency. Expression levels of genes associated with osteoblast differentiation were enhanced following compression, including alkaline phosphatase, osteocalcin, runt‑related transcription factor 2 and osterix. Optimal compression was observed using a magnitude of 0.5 MPa for 6 h, whereas a magnitude of 1 MPa had no effect on osteoblast differentiation, and had a negative effect when applied for prolonged time periods. Compressive loading additionally enhanced the mRNA expression levels of the Wnt/β‑catenin signaling pathway component, low density lipoprotein receptor‑related protein 5, and the protein expression levels of Wnt1, disheveled segment polarity protein‑2 (DVL2) and β-catenin. By contrast, mRNA expression levels of sclerostin and the inactive form of β-catenin (phosphorylated at Ser33/37/Thr41) were reduced following compressive loading. Following compressive loading of cells, dickkopf-related protein 1 (DKK‑1), an inhibitor of the Wnt signaling pathway, increased protein expression levels of the inactive form of the Wnt‑associated protein, phosphorylated‑β‑catenin, compared with compression alone. However, DVL2 and Wnt1 protein expression levels were unaffected, suggesting that the loading‑induced activation of Wnt/β‑catenin signaling decreased however, it was not prevented by DKK‑1 treatment. In conclusion, the present study demonstrated that cyclic compressive load promoted osteoblast differentiation and may be dependent on the Wnt/β-catenin signaling pathway in regard to magnitude and duration.

This study examined the effects of different exercise intensities and durations on bone mineral density (BMD) and bone strength in senescence-accelerated mouse prone 6 (SAMP6) and determined the involvement of the Wnt signaling pathway in exercise-induced osteogenesis. Three-month-old male SAMP6 mice were randomly assigned to different speeds of treadmill running exercise representing low, medium and high intensity, with the duration of five and nine weeks, respectively. We showed that medium-intensity exercise had positive effects on skeletal health, including BMD and bone strength, and the efficacy was higher than that of low-intensity exercise. Interestingly, high-intensity exercise can maintain or even increase bone strength, despite its negative effects on bone mass. Nine weeks of exercise was superior to 5 weeks of exercise, particularly for low-intensity exercise. Furthermore, these effects of exercise-induced osteogenesis are accompanied by activation of the Wnt signaling pathway. Taken together, these results suggest that the positive effects of exercise on osteoporosis prevention are intensity and duration-dependent, and may involve the regulation of Wnt signaling pathways.

As a type of multipotential cells, bone marrow mesenchymal stromal cells (BMMSCs) can differentiate into chondrocytes, osteoblasts, and adipocytes under different loading condition or specific microenvironment. Previous studies have shown that BMMSCs and their lineage-differentiated progeny (for example, osteoblasts), and osteocytes are mechanosensitive in bone. The appropriate physical activity and exercise could help attenuate bone loss, effectively stimulate bone formation, increase bone mineral density (BMD), prevent the progression of osteoporosis, and reduce the risk of bone fractures. Bone morphogenetic protein (BMP) is originally discovered as a protein with heterotopic bone-inducing activity in the bone matrix that exerts a critical role in multiple stages of bone metabolism. In the present study, the medium-intensity treadmill exercise enhanced bone formation and increased osteocalcin (OCN) and osteopontin (OPN) mRNA expression as well as activation of the BMP-Smad signaling pathway in vivo. In order to investigate the effect of a BMP-Smad signaling pathway, we injected mice with activated enzyme inhibitors (LDN-193189HCL) and subjected the mice to treadmill exercise intervention. LDN-193189HCL attenuated the BMD and bone mass mediated by medium-intensity exercise and BMP-Smad signaling pathway.