Early protection against bone stress injuries by mobilization of endogenous targeted bone remodeling.

Bone stress injuries are common overuse injuries, especially in soldiers, athletes, and performers. In contrast to various post-injury treatments, early protection against bone stress injuries can provide greater benefit. This study explored the early protection strategies against bone stress injuries by mobilization of endogenous targeted bone remodeling. The effects of various pharmaceutical/biophysical approaches, individual or combinational, were investigated by giving intervention before fatigue loading. We optimized the dosage and administration parameters and found that early intervention with pulsed electromagnetic field and parathyroid hormone (i.e., PEMF+PTH) resulted in the most pronounced protective effects among all the approaches against the bone stress injuries. In addition, the mechanisms by which the strategy mobilizes targeted bone remodeling and enhances the self-repair capacity of bone were systematically investigated. This study proposes strategies to reduce the incidence of bone stress injuries in high-risk populations (e.g., soldiers and athletes), particularly for those before sudden increased physical training.

Circadian Rhythm Modulates the Therapeutic Activity of Pulsed Electromagnetic Fields on Intervertebral Disc Degeneration in Rats.

Circadian rhythm (CR) imparts significant benefits in treating multiple diseases, such as heart diseases and arthritis. But the CR effect on intervertebral disc degeneration (IVDD) therapy remains unclear. Recent studies revealed that pulsed electromagnetic fields (PEMF) are capable of alleviating IVDD. In this study, we evaluated the CR-mediated regulation of PEMF therapeutic effect on IVDD induced by rat tail disc needle puncture. Our results demonstrated that the daytime PEMF stimulation (DPEMF) is more effective than the nighttime PEMF (NPEMF) in delaying IVDD. Moreover, the rats treated with DPEMF maintained better disc stability and histology after 8 weeks, relative to NPEMF. CR and PEMF cotherapies were also examined in cellular models, whereby serum shock was used to induce different levels of clock gene expression in the nucleus pulposus (NP), thus imitating CR in vitro. PEMF at ZT8 (higher level of clock gene expression) correlated with a higher extracellular matrix (ECM) component expression, compared to ZT20 (lower level of clock gene expression). Taken together, these data suggest a strong role of CR in regulating the beneficial effect of PEMF on IVDD. Our findings provide a potential clinical significance of CR in optimizing PEMF positive effects on IVDD.

Amelioration of bone fragility by pulsed electromagnetic fields in type 2 diabetic KK-Ay mice involving Wnt/ß-catenin signaling.

Type 2 diabetes mellitus (T2DM) results in compromised bone microstructure and quality, and subsequently increased risks of fractures. However, it still lacks safe and effective approaches resisting T2DM bone fragility. Pulsed electromagnetic fields (PEMFs) exposure has proven to be effective in accelerating fracture healing and attenuating osteopenia/osteoporosis induced by estrogen deficiency. Nevertheless, whether and how PEMFs resist T2DM-associated bone deterioration remain not fully identified. The KK-Ay mouse was used as the T2DM model. We found that PEMF stimulation with 2 h/day for 8 wk remarkably improved trabecular bone microarchitecture, decreased cortical bone porosity, and promoted trabecular and cortical bone material properties in KK-Ay mice. PEMF stimulated bone formation in KK-Ay mice, as evidenced by increased serum levels of bone formation (osteocalcin and P1NP), enhanced bone formation rate, and increased osteoblast number. PEMF significantly suppressed osteocytic apoptosis and sclerostin expression in KK-Ay mice. PEMF exerted beneficial effects on osteoblast- and osteocyte-related gene expression in the skeleton of KK-Ay mice. Nevertheless, PEMF exerted no effect on serum biomarkers of bone resorption (TRAcP5b and CTX-1), osteoclast number, or osteoclast-specific gene expression (TRAP and cathepsin K). PEMF upregulated gene expression of canonical Wnt ligands (including Wnt1, Wnt3a, and Wnt10b), but not noncanonical Wnt5a. PEMF also upregulated skeletal protein expression of downstream p-GSK-3ß and ß-catenin in KK-Ay mice. Moreover, PEMF-induced improvement in bone microstructure, mechanical strength, and bone formation in KK-Ay mice was abolished after intragastric administration with the Wnt antagonist ETC-159. Together, our results suggest that PEMF can improve bone microarchitecture and quality by enhancing the biological activities of osteoblasts and osteocytes, which are associated with the activation of the Wnt/ß-catenin signaling pathway. PEMF might become an effective countermeasure against T2DM-induced bone deterioration.NEW & NOTEWORTHY PEMF improved trabecular bone microarchitecture and suppressed cortical bone porosity in T2DM KK-Ay mice. It attenuated T2DM-induced detrimental consequence on trabecular and cortical bone material properties. PEMF resisted bone deterioration in KK-Ay mice by enhancing osteoblast-mediated bone formation. PEMF also significantly suppressed osteocytic apoptosis and sclerostin expression in KK-Ay mice. The therapeutic potential of PEMF on T2DM-induced bone deterioration was associated with the activation of Wnt/ß-catenin signaling.

[Dendritic cell tumor vaccine assisted by Tiaohengfang polysaccharides enhances immune function of S180 tumor-bearing mice and inhibits tumor growth].

Objective To investigate the immunotherapeutic effect and mechanism of dendritic cell (DC) vaccine assisted by Tiaohengfang polysaccharides (ThPP) in S180 tumor-bearing mice. Methods Mouse bone marrow-derived cells were cultured in vitro and mature DCs were obtained with the assistance of cytokines and ThPP. The expression of CD80 and CD86 of DCs induced by ThPP was examined, and S180 tumor cells were used as antigens to stimulate dendritic cells to become dendritic cell tumor vaccine. Tumor-bearing models were established in mice by S180 tumor cells inoculated into the armpit of the left forelimb, and the mice were randomly divided into four groups according to body mass, namely tumor-bearing blank group, positive control group (cyclophosphamide), dendritic cell vaccine group adjuvanted by ThPP and TNF-α. The tumor-bearing mice were treated on the 5th and 10th days after inoculation of tumor cells. The tumor-bearing mice were killed on the 12th day and the tumor inhibition was observed by the tumor mass detection. At the same time, peritoneal macrophages were isolated and cultured, and the expression of CD11b and IL-12 were measured by immunohistochemistry. The levels of serum IL-12 and TNF-α in the mice were detected by ELISA. The survival time of the other four groups of tumor-bearing mice was observed after treatment with the same method. Results The expression of CD80 and CD86 in the TNF-α group and ThPP group were higher than those in the blank control group, and the ThPP group was more significant. The tumor inhibition rate and survival extension period of ThPP, TNF-α and positive groups were significantly higher than those of the model blank group. The levels of serum IL-12 and TNF-α in the ThPP group were higher than those in the positive cyclophosphamide group and model black group. There was no significant difference between the ThPP group and TNF-α group. The expression of CD11b in the macrophages of ThPP group was lower than that in the model blank group and positive group, while the expression of IL-12 in the macrophages of ThPP group was higher than that in the model blank group and positive group, without significant difference compared with TNF-α group. Conclusion ThPP-adjuvanted DC tumor vaccine can inhibit tumor growth and prolong survival time of S180 tumor-bearing mice, which is related to promoting the maturation of DCs and increasing the secretion of IL-12 and TNF-α.