Icariin, the main active compound of the traditional Chinese medicine, Epimedium, is commonly used for the clinical treatment of osteoporosis. However, the precise molecular mechanism of the therapeutic effect of icariin has not been elucidated. The aim of this study was to examine the effect of icariin on cell viability, alkaline phosphatase (ALP) activity, the amount of calcified nodules, and to delineate the molecular mechanism of icariin-enhanced bone formation by investigating the expression of bone morphogenic protein-2 (BMP-2), Smad4, Cbfa1/Runx2, osteoprotegerin (OPG), receptor activator of nuclear factor κ-B ligand (RANKL) and the OPG/RANKL ratio in the hFOB 1.19 human osteoblastic cell line. We found that icariin significantly increased the cell viability, the activity of ALP and the amount of calcified nodules in the hFOB 1.19 cells. Furthermore, we observed that icariin upregulated the expression of BMP-2, Smad4, Cbfa1/Runx2, OPG, RANKL and the OPG/RANKL ratio. Our results indicate that icariin can modulate the process of bone formation via the BMP-2/Smad4 signal transduction pathway in hFOB 1.19 cells.

Achyranthes bidentata polysaccharides (ABPS) are the active components of Radix Achyranthis Bidentatae (AB), which has been extensively used in Traditional Chinese medicine (TCM) in the treatment of osteoarthritis (OA). Our previous study provided evidence that ABPS regulated the G1/S transition to promote chondrocyte proliferation. However, the precise mechanisms involved remain to be elucidated. In the present study, we aimed to investigate the effects of ABPS on the Wnt/β‑catenin signaling pathway in chondrocytes. Chondrocytes, obtained from the knee cartilage of Sprague-Dawley rats, were identified by type II collagen immunohistochemistry. ABPS upregulated the expression of Wnt-4, Frizzled-2, β-catenin and cyclin D1, and downregulated the expression of glycogen synthase kinase 3β (GSK-3β), as shown by reverse transcription PCR (RT-PCR) and western blot analysis. Using immunofluorescence, we also found that ABPS induced β-catenin nuclear translocation. Importantly, the expression of β-catenin and cyclin D1 was partly inhibited by Dickkopf-1 (DKK-1), an inhibitor of the Wnt/β-catenin signaling pathway. In addition, we found that ABPS increased the expression of type II collagen in chondrocytes. These results suggest that ABPS promote chondrocyte proliferation by activating the Wnt/β-catenin signaling pathway.

Background: Dorsal mesenchymal protrusion (DMP) is required for cardiac septation, but its additional functions are unknown. Results: Shox2 is required for the nodal-like characteristics and development of embryonic DMP by regulating BMP/Smad4 signaling pathway. Conclusion: A Shox2-BMP genetic cascade regulates DMP development and its temporal pacemaking function. Significance: A novel function of DMP and its developmental regulatory mechanism are identified.

The temporomandibular joint (TMJ) consists of the glenoid fossa arising from the otic capsule through intramembranous ossification, the fibrocartilaginous disc and the condyle, derived from the secondary cartilage by endochondral ossification. We have reported previously that cranial neural crest-specific inactivation of the homeobox gene Shox2, which is expressed in the mesenchymal cells of maxilla-mandibular junction and later in the progenitor cells and perichondrium of the developing chondyle, led to dysplasia and ankylosis of the TMJ, and replacement of the mouse Shox2 with the human SHOX gene rescued the dysplastic and ankylosis phenotypes but developed a prematurely worn out articular disc. In this study, we investigated the molecular and cellular bases for the premature wear out articular disc in the TMJ of mice carrying the human SHOX replacement allele in the Shox2 locus (referred as Shox2SHOX-KI/KI). We found that the developmental process and expression of several key genes in the TMJ of Shox2SHOX-KI/KI mice appeared similar to the controls. However, the disc of the Shox2SHOX-KI/KI TMJ exhibited a reduced level of Col I and Aggrecan, accompanied by increased activities of matrix metalloproteinases (MMPs) and a down-regulation of Ihh expression. Dramatically increased cell apoptosis in the disc was also observed. These combinatory cellular and molecular defects appear to contribute to the observed disc phenotype, suggesting that while the human SHOX can exert similar function as the mouse Shox2 in regulating early TMJ development, it apparently has a distinct function in the regulation of those molecules that are involved in tissue homeostasis.