Alterations in the microenvironment and the effects produced of TRPV5 in osteoporosis.

The pathogenesis of osteoporosis involves multiple factors, among which alterations in the bone microenvironment play a crucial role in disrupting normal bone metabolic balance. Transient receptor potential vanilloid 5 (TRPV5), a member of the TRPV family, is an essential determinant of the bone microenvironment, acting at multiple levels to influence its properties. TRPV5 exerts a pivotal influence on bone through the regulation of calcium reabsorption and transportation while also responding to steroid hormones and agonists. Although the metabolic consequences of osteoporosis, such as loss of bone calcium, reduced mineralization capacity, and active osteoclasts, have received significant attention, this review focuses on the changes in the osteoporotic microenvironment and the specific effects of TRPV5 at various levels.

Pulse Electromagnetic Field for Treating Postmenopausal Osteoporosis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Postmenopausal osteoporosis is a type of chronic disease with high morbidity and high economic burden. Due to the adverse effects of long-term drug therapy, physical therapy, such as pulsed electromagnetic fields (PEMF), is widely implemented in clinical practice. Therefore, we first conducted the meta-analysis on the efficacy and safety of PEMF in the treatment of postmenopausal osteoporosis. We searched eight databases to acquire potentially eligible studies. Outcome indicators include bone mineral density (BMD), visual analogue scale (VAS), biochemical markers of alkaline phosphatase (ALP), osteocalcin, bone-specific alkaline phosphatase (BSAP), type I collagen carboxy-terminal peptide (CTX), and adverse events. The results showed that a total of 19 studies (1303 patients) were retrieved from eight databases. Compared with conventional medications, PEMF combined with conventional medications significantly increased BMD of lumbar vertebra, femoral, Ward's triangle, bone-specific biochemical indicators of ALP, BSAP, and osteocalcin, and relieved pain. However, The incidence of adverse events was not statistically significant between PEMF combined with conventional medications and conventional medications alone. Compared with conventional medications, PEMF significantly increased the BMD of the femur and reduced the degree of pain, but there was no statistical difference in the BMD of the lumbar spine between PEMF and placebo. Except osteocalcin, BSAP, CTX, and ALP showed no significant difference. In view of its efficacy and safety, PEMF intervention can be considered as a potentially effective complementary therapy for postmenopausal women with osteoporosis. © 2022 Bioelectromagnetics Society.

pH-Responsive Mesoporous Silica Nanoparticles Loaded with Naringin for Targeted Osteoclast Inhibition and Bone Regeneration.

Background: It is well-established that osteoclast activity is significantly influenced by fluctuations in intracellular pH. Consequently, a pH-sensitive gated nano-drug delivery system represents a promising therapeutic approach to mitigate osteoclast overactivity. Our prior research indicated that naringin, a natural flavonoid, effectively mitigates osteoclast activity. However, naringin showed low oral availability and short half-life, which hinders its clinical application. We developed a drug delivery system wherein chitosan, as gatekeepers, coats mesoporous silica nanoparticles loaded with naringin (CS@MSNs-Naringin). However, the inhibitory effects of CS@MSNs-Naringin on osteoclasts and the underlying mechanisms remain unclear, warranting further research. Methods: First, we synthesized CS@MSNs-Naringin and conducted a comprehensive characterization. We also measured drug release rates in a pH gradient solution and verified its biosafety. Subsequently, we investigated the impact of CS@MSNs-Naringin on osteoclasts induced by bone marrow-derived macrophages, focusing on differentiation and bone resorption activity while exploring potential mechanisms. Finally, we established a rat model of bilateral critical-sized calvarial bone defects, in which CS@MSNs-Naringin was dispersed in GelMA hydrogel to achieve in situ drug delivery. We observed the ability of CS@MSNs-Naringin to promote bone regeneration and inhibit osteoclast activity in vivo. Results: CS@MSNs-Naringin exhibited high uniformity and dispersity, low cytotoxicity (concentration≤120 µg/mL), and significant pH sensitivity. In vitro, compared to Naringin and MSNs-Naringin, CS@MSNs-Naringin more effectively inhibited the formation and bone resorption activity of osteoclasts. This effect was accompanied by decreased phosphorylation of key factors in the NF-κB and MAPK signaling pathways, increased apoptosis levels, and a subsequent reduction in the production of osteoclast-specific genes and proteins. In vivo, CS@MSNs-Naringin outperformed Naringin and MSNs-Naringin, promoting new bone formation while inhibiting osteoclast activity to a greater extent. Conclusion: Our research suggested that CS@MSNs-Naringin exhibited the strikingly ability to anti-osteoclasts in vitro and in vivo, moreover promoted bone regeneration in the calvarial bone defect.

Effects and mechanisms of microenvironmental acidosis on osteoclast biology.

Due to continuous bone remodeling, the bone tissue is dynamic and constantly being updated. Bone remodeling is precisely regulated by the balance between osteoblast-induced bone formation and osteoclast-induced bone resorption. As a giant multinucleated cell, formation and activities of osteoclasts are regulated by macrophage colony-stimulating factor (M-CSF), receptor activator of nuclear factor-kappaB ligand (RANKL), and by pathological destabilization of the extracellular microenvironment. Microenvironmental acidosis, as the prime candidate, is a driving force of multiple biological activities of osteoclast precursor and osteoclasts. The mechanisms involved in these processes, especially acid-sensitive receptors/channels, are of great precision and complicated. Recently, remarkable progress has been achieved in the field of acid-sensitive mechanisms of osteoclasts. It is important to elucidate the relationship between microenvironmental acidosis and excessive osteoclasts activity, which will help in understanding the pathophysiology of diseases that are associated with excess bone resorption. This review summarizes physiological consequences and in particular, potential mechanisms of osteoclast precursor or osteoclasts in the context of acidosis microenvironments.

Data Mining and Network Pharmacology Analysis of Kidney-Tonifying Herbs on the Treatment of Renal Osteodystrophy Based on the Theory of "Kidney Governing Bones" in Traditional Chinese Medicine.

Background: Renal osteodystrophy (ROD) secondary to chronic kidney disease is closely associated with osteoporosis and fractures. Based on the theory of "kidney governing bones" in traditional Chinese medicine (TCM), treating bone diseases from the perspective of the kidney has become a basic principle of treating ROD. However, there are many kidney-tonifying herbs and their mechanisms of treating ROD are not clear. Therefore, our study intends to use data mining and network pharmacology to study the commonly used kidney-tonifying herbs, as well as their active ingredients and mechanisms of treating ROD. Methods: We established a clinical ROD database by searching PubMed, CNKI, and other databases and screened out a core herbal combination of treating ROD. Furthermore, by using databases such as Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and GeneCards, we obtained active ingredients and targets of the core herbal combination and ROD targets. The STRING website and Cytoscape software were then used to obtain information on key active ingredients and key targets. Finally, we conducted GO and KEGG analyses using the Metascape website and molecular docking using the AutoDock Vina software. Results: Our study eventually included 58 prescriptions and 116 herbs of treating ROD. Through data mining, we found that yin-yang-huo, du-zhong, and bu-gu-zhi (YDB) constituted a core herbal combination to treat ROD. Network pharmacology showed that YDB mainly acted on targets such as estrogen receptor alpha through active ingredients such as quercetin by mitogen-activated protein kinase and other signaling pathways. Conclusion: Many ingredients, targets, and pathways are involved in the treatment of YDB for ROD. Specifically, the flavonoids contained in YDB have great potential for ROD treatment.

Efficacy and Safety of Acupuncture Therapy for Patients with Acute Ankle Sprain: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: The efficacy of acupuncture for acute ankle sprain (AAS) is controversial. This study aimed to critically assess the efficacy and safety of acupuncture for AAS. METHODS: Parallel-group randomized controlled trials (RCTs) were included regardless of language or publication date. Participants with AAS were included regardless of age, sex, race, nationality, or diagnostic criteria for AAS. Experimental interventions included acupuncture alone or in combination with traditional therapies. Control interventions included no treatment, placebo, or traditional therapies. The primary outcome was the Kofoed ankle score. The secondary outcomes included visual analogue scale, duration of pain, use of painkiller, ankle circumference, effective rate, cure rate, and adverse events. PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang Digital Periodicals, and Chinese Science and Technology Periodicals database were searched to identify potentially eligible studies from inception to September 10, 2020. World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), ClinicalTrials.gov, Chinese Clinical Trial Registry (ChiCTR), and the reference list of eligible RCTs were checked to identify ongoing or unpublished studies. Risk of bias was assessed by the Cochrane Collaboration's tool. Statistical analyses were performed by RevMan 5.3 software. P < 0.05 indicated statistical significance. RESULTS: Seventeen eligible studies were included for the statistical analysis. There was no statistically significant difference of Kofoed ankle score between acupuncture and Rest, Ice, Compression, and Elevation (RICE) group (P=0.75). However, acupuncture could significantly relieve pain (P=0.02) and increase cure rate (P=0.004) compared with RICE. Moreover, acupuncture plus RICE could also significantly relieve pain (P < 0.00001) and increase cure rate (P=0.01) compared with RICE alone. Acupuncture combined with massage could significantly relieve pain (P=0.04) compared with massage alone. Acupuncture plus Chinese medicine might be more effective for relieving pain (P < 0.00001), reducing the duration of pain (P < 0.00001), and increasing cure rate (P=0.0002) compared with Chinese medicine alone. Two studies reported no adverse reactions. One study reported that a participant suffered from mild drug-related allergic reaction and was healed without treatment. CONCLUSIONS: The findings of the present study suggest that acupuncture may be beneficial for AAS. However, more large-scale and well-designed RCTs are warranted.