mendelian-randomization-transcriptomics-network-pharmacology-for

Mendelian Randomization Transcriptomics and Network Pharmacology for Identification of Osteoarthritis Drug Targets

This article delineates an integrated methodology that combines Mendelian randomization (MR), transcriptomic analysis, and network pharmacology to ...

Nanchang Hongdu Hospital of Traditional Chinese Medicine

Tendon injury is a prevalent orthopedic disease that currently lacks effective treatment. Galangin (GLN) is a vital flavonoid found abundantly in galangal and is known for its natural activity. This study aimed to investigate the GLN-mediated molecular mechanism of tendon-derived stem cells (TDSCs) in tendon repair. The TDSCs were characterized using alkaline phosphatase staining, alizarin red S staining, oil red O staining, and flow cytometry. The effect of GLN treatment on collagen deposition was evaluated using Sirius red staining and quantitative (q)PCR, while a Western bot was used to assess protein levels and analyze pathways. Results showed that GLN treatment not only increased the collagen deposition but also elevated the mRNA expression and protein levels of multiple tendon markers like collagen type I alpha 1 (COL1A1), decorin (DCN) and tenomodulin (TNMD) in TDSCs. Moreover, GLN was also found to upregulate the protein levels of transforming growth factor β1 (TGF-β1) and p-Smad3 to activate the TGF-β1/Smad3 signaling pathway, while GLN mediated collagen deposition in TDSCs was reversed by LY3200882, a TGF-β receptor inhibitor. The study concluded that GLN-mediated TDSCs enhanced tendon repair by activating the TGF-β1/Smad3 signaling pathway, suggesting a novel therapeutic option in treating tendon repair.

Galangin Promotes Tendon Repair Mediated by Tendon-Derived Stem Cells through Activating the TGF-β1/Smad3 Signaling Pathway.

Amentoflavone (AF), a plant biflavone isolated from Selaginella sinensis ethanol extract, is characterized by anti-inflammatory and anti-oxidant properties. According to previous studies, inflammation and oxidative stress are closely related to the pathophysiology of osteoarthritis (OA). However, the effects and mechanisms of AF on OA have not been elucidated.To investigate the inhibitory effects and its molecular mechanism of AF on extracellular matrix (ECM) degradation stimulated by IL-1β as well as subchondral bone loss induced by RANKL in mice chondrocytes. Quantitative PCR was used to detect the mRNA expression of genes related to inflammation, ECM, and osteoclast differentiation. Protein expression level of iNOS, COX-2, MMP13, ADAMTS5, COL2A1, SOX9, NFATc1, c-fos, JNK, ERK, P65, IκBα was measured by western blotting. The levels of TNF-α and IL-6 in the supernatants were measured by ELISA. The amount of ECM in chondrocytes was measured using toluidine blue staining. The levels of Aggrecan and Col2a1 in chondrocytes were measured using immunofluorescence. Tartrate-resistant acid phosphatase (TRAP) staining, F-actin staining and immunofluorescence were used to detect the effect of AF on osteoclast differentiation and bone resorption. The effect of AF on destabilization of the medial meniscus (DMM)-induced OA mice can be detected in hematoxylin-eosin (H&E) staining, Safranin O green staining and immunohistochemistry.AF might drastically attenuated IL-1β-stimulated inflammation and reduction of ECM formation by blocking ERK and NF-κB signaling pathways in chondrocytes. Meanwhile, AF suppressed the formation of osteoclasts and the resorption of bone function induced by RANKL. In vivo, AF played a protective role by stabilizing cartilage ECM and inhibiting subchondral bone loss in destabilization of the medial meniscus (DMM)-induced OA mice, further proving its protective effect in the development of OA. Our study show that AF alleviated OA by suppressing ERK, JNK and NF-κB signaling pathways in OA models in vitro and DMM-induced OA mice, suggesting that AF might be a potential therapeutic agent in the treatment of OA.

Amentoflavone maintaining extracellular matrix homeostasis and inhibiting subchondral bone loss in osteoarthritis by inhibiting ERK, JNK and NF-κB signaling pathways.

To explore effectiveness of arthroscopic Eden-Hybinette procedure with Triple-Pulley and four point anti-rotation fixation technique in the treatment of recurrent anterior dislocation of shoulder joint.

[Arthroscopic Eden-Hybinette procedure with Triple-Pulley and four point anti-rotation fixation technique for recurrent anterior dislocation of shoulder joint].

Deep vein thrombosis (DVT) is a significant postoperative complication in patients with lower limb fractures, potentially leading to life-threatening outcomes such as pulmonary embolism. This study aimed to evaluate the knowledge, attitudes, and practices (KAP) of this high-risk population regarding DVT prevention. A cross-sectional study was conducted at Nanchang Hongdu Hospital of Traditional Chinese Medicine between March 2023 and May 2024. A structured questionnaire collected demographic and KAP data, analyzed using descriptive statistics and structural equation modeling (SEM). Among 442 valid respondents, SEM revealed direct effects of knowledge on attitudes (β = 0.593, P < 0.001) and attitudes on practices (β = 0.746, P < 0.001). Despite proactive practices, patients demonstrated inadequate knowledge and negative attitudes towards DVT. These findings underscore the need for targeted educational interventions to enhance patient understanding and attitudes, ultimately improving preventive behaviors and reducing DVT-related complications.

Knowledge, attitudes, and practices of patients with lower limb fractures post-surgery regarding deep vein thrombosis.

Excessive activation of osteoclasts plays a pivotal role in the pathophysiology of osteoporosis, which is predominantly characterized by bone resorption. However, therapeutic strategies targeting osteoclasts remain limited. In this study, we investigated the inhibitory effects of Epimedin B (EB) on osteoclastogenesis and its potential anti-osteoporotic properties. An ex vivo osteoclast differentiation model was established using BMMs. Osteoclastogenesis was assessed via TRAP staining and F-actin ring formation. Hydroxyapatite bone plates were employed to evaluate the impact of EB on bone resorption function. Network pharmacology predictions combined with transcriptomic analysis were employed to untangle the signaling pathways and targets regulated by EB. Cellular thermal shift assays were performed to validate EB-interacting proteins. The expression levels of osteoclast-specific and ROS-related proteins/genes, as well as phosphorylation changes in signaling pathways, were quantified by Western blot and RT-PCR. Protein expression and mitochondrial ROS levels were detected by fluorescence staining, while intracellular ROS generation was measured via flow cytometry. An ovariectomized (OVX) mouse model of osteoporosis was established to evaluate the bone-protective effects and in vivo mechanisms of EB. The results demonstrated that EB significantly suppressed RANKL-induced osteoclast differentiation, particularly during the early phase and cytoskeletal organization stage, while also inhibiting bone resorption activity in mature osteoclasts. Mechanistic studies revealed that EB directly binds to ESR1 and protects it from degradation. Furthermore, EB was found to downregulate the expression of osteoclast-specific genes/proteins and inhibit the phosphorylation of MAPK and PI3K-AKT pathways. Furthermore, EB activated the AMPK pathway, subsequently initiating the Nrf2-mediated antioxidant system, leading to reduced ROS levels. Notably, EB markedly rescued ovariectomy-induced bone loss, with efficacy comparable to estrogen therapy, an effect associated with suppressed osteoclast activity and AMPK pathway activation. These findings provide, for the first time, novel theoretical evidence and a potential therapeutic strategy for EB in the prevention and treatment of osteoporosis.

Epimedin B attenuates ovariectomy-induced bone loss by suppressing osteoclastogenesis through decreasing ROS production and targeting ESR1.

To investigate effectiveness of arthroscopic superior capsular reconstruction using a "sandwich" patch combined with platelet-rich plasma (PRP) injection in treating massive irreparable rotator cuff tears.

[Effectiveness of arthroscopic superior capsular reconstruction using a "sandwich" patch combined with platelet-rich plasma injection in treating massive irreparable rotator cuff tears].

Article	Year
Galangin Promotes Tendon Repair Mediated by Tendon-Derived Stem Cells through Activating the TGF-β1/Smad3 Signaling Pathway. Chemical & pharmaceutical bulletin\| PubMed ID: 39010213	2024
Amentoflavone maintaining extracellular matrix homeostasis and inhibiting subchondral bone loss in osteoarthritis by inhibiting ERK, JNK and NF-κB signaling pathways. Journal of orthopaedic surgery and research\| PubMed ID: 39407273	2024
[Arthroscopic Eden-Hybinette procedure with Triple-Pulley and four point anti-rotation fixation technique for recurrent anterior dislocation of shoulder joint]. Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery\| PubMed ID: 39694832	2024
Knowledge, attitudes, and practices of patients with lower limb fractures post-surgery regarding deep vein thrombosis. Scientific reports\| PubMed ID: 40108272	2025
Epimedin B attenuates ovariectomy-induced bone loss by suppressing osteoclastogenesis through decreasing ROS production and targeting ESR1. Free radical biology & medicine\| PubMed ID: 40834910	2025
[Effectiveness of arthroscopic superior capsular reconstruction using a "sandwich" patch combined with platelet-rich plasma injection in treating massive irreparable rotator cuff tears]. Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery\| PubMed ID: 41093793	2025

Shaoyong Fan

Biography

JoVE Journal Publications

Other Publications