Exploring the multicomponent synergy mechanism of Zuogui Wan on postmenopausal osteoporosis by a systems pharmacology strategy.

OBJECTIVE: To explore the multi-component synergistic mechanism of Zuogui Wan (, ZGW) in treating postmenopausal osteoporosis (PMOP). METHODS: The main components and target genes of ZGW were screened via the Traditional Chinese Medicine Systems Pharmacology (TCMSP). In addition, the target gene sets of PMOP were derived from the GeneCards and Online Mendelian Inheritance in Man databases. The search tool for recurring instances of neighbouring genes (STRING) 11.0 software was used to analyze the interaction among intersecting genes. Cytoscape 3.6.1 software and the Matthews correlation coefficient (MCC) algorithm were used to screen the core genes. Fifty Sprague-Dawley female rats were randomly divided into the sham-operated (Sham) group and the four ovariectomized (OVX) subgroups. Rats subjected to Sham or OVX were administered with the vehicle (OVX, 1 mL water/100 g weight), 17ß-estradiol (E2, 50 µg·kg-1·d-1), and lyophilized powder of ZGW at a low dose of 2.3 (ZGW-L) and high dose of 4.6 (ZGW-H) g·kg-1·d-1 for three months. The bone density and bone strength were assessed using dual-energy X-ray and three-point bending tests, respectively. Furthermore, enzyme-linked immun-osorbent assay, Hematoxylin-eosin staining, and western blot analysis were used to determine the potential pharmacological mechanisms of action of ZGW in PMOP. RESULTS: A total of 117 active compounds of ZGW were screened from the TCMSP. Furthermore, 108 intersecting genes of drugs and diseases were identified. Using STRING software and the MCC algorithm, ten core genes, including C-X-C chemokine living 8 (CXCL8), C-C chemokine receptor type 2 (CCR2), alpha-2a active receptor (ADRA2A), melatonin receptor type 1B (MTNR1B), and amyloid-beta A4 protein (APP), were identified. The anti-osteoporosis regulation network of ZGW was constructed using the Cytoscape software. The animal experiments demonstrated that ZGW groups significantly reduced the serum levels of ß-C-terminal telopeptide of type I collagen (ß-CTX) and increased serum levels of bone-specific alkaline phosphatase (BALP) (P < 0.05, P < 0.01). The OVX group exhibited a significant decrease in bone mineral density and bone strength compared with the Sham group (P < 0.01). Moreover, treatment with ZGW resulted in increased trabecular thickness, improved arrangement of trabecular structure, and reduced empty bone lacunae. Furthermore, treatment with ZGW significantly increased the protein expression of CXCL8, ADRA2A, and CCR2 (P < 0.05, P < 0.01), and significantly decreased the protein expression of Runx2 (P < 0.01). Furthermore, the ZGW and E2 groups demonstrated significantly increased BMD (P < 0.05, P < 0.01), improved bone strength (P < 0.05, P < 0.01), reduced expression of CXCL8, ADRA2A, and CCR2, and increased runt-related transcription factor 2 levels in bone tissue (P < 0.05, P < 0.01) compared with the OVX group. However, there were no significant differences in MTNR1B and APP expression among the groups. CONCLUSION: ZGW shows synergistic mechanisms in PMOP through multiple components, targets, and pathways.

The mechanism of oxytocin and its receptors in regulating cells in bone metabolism.

Oxytocin (OT) is a neuropeptide known to affect social behavior and cognition. The epigenetic modification of the oxytocin receptor (OTR) via DNA methylation stimulates parturition and breast milk secretion and inhibits craniopharyngioma, breast cancer, and ovarian cancer growth significantly as well as directly regulates bone metabolism in their peripheral form rather than the central form. OT and OTR can be expressed on bone marrow mesenchymal stem cells (BMSCs), osteoblasts (OB), osteoclasts (OC), osteocytes, chondrocytes, and adipocytes. OB can synthesize OT under the stimulation of estrogen as a paracrine-autocrine regulator for bone formation. OT/OTR, estrogen, and OB form a feed-forward loop through estrogen mediation. The osteoclastogenesis inhibitory factor (OPG)/receptor activator of the nuclear factor kappa-B ligand (RANKL) signaling pathway is crucially required for OT and OTR to exert anti-osteoporosis effect. Downregulating the expression of bone resorption markers and upregulating the expression of the bone morphogenetic protein, OT could increase BMSC activity and promote OB differentiation instead of adipocytes. It could also stimulate the mineralization of OB by motivating OTR translocation into the OB nucleus. Moreover, by inducing intracytoplasmic Ca2+ release and nitric oxide synthesis, OT could regulate the OPG/RANKL ratio in OB and exert a bidirectional regulatory effect on OC. Furthermore, OT could increase the activity of osteocytes and chondrocytes, which helps increase bone mass and improve bone microstructure. This paper reviews recent studies on the role of OT and OTR in regulating cells in bone metabolism as a reference for their clinical use and research based on their reliable anti-osteoporosis effects.

Application of absorbable anchor combined with Kirschner wire in reconstruction of extension function of old mallet finger / 中国修复重建外科杂志

OBJECTIVE@#To investigate the feasibility and effectiveness of absorbable anchor combined with Kirschner wire fixation in the reconstruction of extension function of old mallet finger.@*METHODS@#Between January 2020 and January 2022, 23 cases of old mallet fingers were treated. There were 17 males and 6 females with an average age of 42 years (range, 18-70 years). The cause of injury included sports impact injury in 12 cases, sprain in 9 cases, and previous cut injury in 2 cases. The affected finger included index finger in 4 cases, middle finger in 5 cases, ring finger in 9 cases, and little finger in 5 cases. There were 18 patients of tendinous mallet fingers (Doyle type Ⅰ), 5 patients were only small bone fragments avulsion (Wehbe type ⅠA). The time from injury to operation was 45-120 days, with an average of 67 days. The patients were treated with Kirschner wire to fix the distal interphalangeal joint in a mild back extension position after joint release. The insertion of extensor tendon was reconstructed and fixed with absorbable anchors. After 6 weeks, the Kirschner wire was removed, and the patients started joint flexion and extension training.@*RESULTS@#The postoperative follow-up ranged from 4 to 24 months (mean, 9 months). The wounds healed by first intention without complications such as skin necrosis, wound infection, and nail deformity. The distal interphalangeal joint was not stiff, the joint space was good, and there was no complication such as pain and osteoarthritis. At last follow-up, according to Crawford function evaluation standard, 12 cases were excellent, 9 cases were good, 2 cases were fair, and the good and excellent rate was 91.3%.@*CONCLUSION@#Absorbable anchor combined with Kirschner wire fixation can be used to reconstruct the extension function of old mallet finger, which has the advantages of simple operation and less complications.