The present study was designed to explore the relationship between neovascularization, hypertrophic cartilage and the microstructural properties of cancellous bone in adult rat's condyle in response to mechanical strain produced by mandibular advancement.Seventy-eight 120-day-old female Sprague-Dawley rats were randomly allotted to six groups, nine animals in each experimental group according to different time points. Mandibular advancement appliances were used to produce mechanical strain onto to the mandibular condyles of rats. Immunostaining of VEGF and type X collagen were carried out. Tartrate-Resistant Acid Phosphatase (TRAP) reaction was used to assess the activity of chondroclasts. Direct three-dimensional morphometric analysis was carried out with microcomputed tomography (Micro-CT) scanning to evaluate the properties of microstructure of cancellous bone in the mandibular condyles. Results showed that mechanical strain produced by mandibular advancement induced neovascularization in the posterior condyle marked by the increased expression of VEGF. Neovascularization coupled the remodeling of calcified cartilage as marked by the expression of type X collagen and new bone formation. The new bone formed in the adult condyle was characterized by thinner trabecular thickness, more trabecular number and increased trabecular space. In conclusion, mechanical strain produced by mandibular advancement induces neovascularization and osteogenesis leading to adaptive growth of condyle in adult rats.

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Background: Osteoarthritis is a disabling disease, which seriously affects the quality of life of patients. Increasing evidence has indicated that Chinese herbal medicine including Eucommia ulmoides (EU) and Radix Achyranthis Bidentatae (RAB) have potential in the treatment of osteoarthritis, and this is associated with their multitarget and multi-link action characteristics. Although their potential anti-arthritic activity has been reported, the exact mechanism of EU-RAB action in osteoarthritis remains unexplored. Therefore, this study explores the mechanism of EU-RAB against osteoarthritis using network pharmacology and molecular docking technology. Methods: Public databases including TCMSP、BATMAN-TCM、OMIM and Genecards were used to predict the bioactive ingredients and putative targets of EU-RAB against osteoarthritis. Enrichment analysis was performed to expound the biological functions and associated pathways of the hub targets. Cytoscape software was used to construct a "compounds-targets-pathways" network for elucidating the comprehensive molecular mechanism of EU-RAB against osteoarthritis. Molecular docking was used to verify the correlation between the main active ingredients and hub targets. Results: Network pharmacological analysis of EU-RAB in the treatment of osteoarthritis, identified 50 active ingredients including quercetin, kaempferol, wogonin, and baicalein with important biological effect. A total of 68 key targets were screened, including IL-6, EGFR, MAPK8, etc., and they were found to be enriched in a series of signaling pathways, such as apoptosis, TNF, MAPK, PI3K/AKT, and IL-17 signaling pathways. Moreover, molecular docking analysis showed that the main ingredients were tightly bound to the core targets, further confirming the anti-arthritic effects.

<b><i>Background:</i></b> Osteoarthritis (OA) is the most common joint disorder characterized by degeneration of the articular cartilage and joint destruction with an associated risk of mobility disability in elderly people. Although a lot of achievements have been made, OA is still regarded as an incurable disease. Therefore, the pathological mechanisms and novel therapeutic strategies of OA need more investigation. <b><i>Methods:</i></b> MTT assay was conducted to measure the viability of chondrocytes after LPS treatment. Cell apoptosis was analyzed by annexin V/propidium iodide labeling. ELISA was used to determine the concentrations of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α in the culture supernatant of chondrocytes. The expression level of miR-155, IL-1β, FOXO3, TNF-α, IL-6, caspase-3, and caspase-9 in chondrocytes was analyzed by RT-qPCR or Western blot. <b><i>Results:</i></b> We found that LPS led to inflammatory responses, cell apoptosis, and increased miR-155 expression in human articular chondrocytes. Tanshinone IIA could inhibit LPS-induced inflammation and cell apoptosis of chondrocytes via regulating the expression of miR-155 and FOXO3. miR-155 directly targeted the 3′-UTR of FOXO3 to regulate its expression. <b><i>Conclusions:</i></b> Taken together, our data suggest tanshinone IIA ameliorates inflammation response in OA via inhibition of the miR-155/FOXO3 axis, and provide some evidences that tanshinone IIA could be designed and developed as a new promising clinical therapeutic drug for OA patients.

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