Icariin has been mostly reported to enhance bone fracture healing and treat postmenopausal osteoporosis in ovariectomized animal model. As another novel animal model of osteoporosis, there is few publication about the effect of Icariin on osteoprotegerin-deficient mice. Therefore, the goal of this study is to find the effect on bone formation and underlying mechanisms of Icariin in osteoprotegerin (OPG) knockout (KO) mice. We found that Icariin significantly stimulated new bone formation after local injection over the surface of calvaria at the dose of 5 mg/kg per day. With this dose, Icariin was also capable of significantly reversing OPG-deficient-induced bone loss and bone strength reduction. Real-time PCR analysis showed that Icariin significantly upregulated the expression of BMP2, BMP4, RUNX2, OC, Wnt1, and Wnt3a in OPG KO mice. Icariin also significantly increased the expression of AXIN2, DKK1, TCF1, and LEF1, which are the direct target genes ofβ-catenin signaling. The in vitro studies showed that Icariin induced osteoblast differentiation through the activation of Wnt/β-catenin-BMP signaling by in vitro deletion of theβ-catenin gene usingβ-cateninfx/fxmice. Together, our findings demonstrate that Icariin significantly reverses the phenotypes of OPG-deficient mice through the activation of Wnt/β-catenin-BMP signaling.

The systematicness of phenomics and Traditional Chinese Medicine (TCM) enable these two disciplines to interlink with each other. This article discussed the similarity in theory and application between TCM and phenomics and illustrates their respective advantages in diagnosis and treatment of diseases, forming a new discipline eventually. Chinese medicine phenomics (Chinmedphenomics) is built on classic TCM, combined with phenomics technology, and the development of which needs the mega cohort with TCM syndrome and the characteristics of precision medicine as well as multi-disciplinary cooperation, which is personalized, precise and promising, providing unique scientific insights into understanding human health.

Background: Osteoporosis is a metabolic disease, and osteoporotic fracture (OPF) is one of its most serious complications. It is often ignored that the influence of the muscles surrounding the fracture on the healing of OPF. We aimed to clarify the role of skeletal muscle satellite cells (SMSCs) in promoting OPF healing by β‐catenin, to improve our understanding of SMSCs, and let us explore its potential as a therapeutic target.Methods: Skeletal muscles were obtained from control non‐OPF or OPF patients for primary SMSCs culture (n = 3, 33% females, mean age 60 ± 15.52). Expression of SMSCs was measured. In vivo, 3‐month‐old female C57BL/6 mice underwent OVX surgery. Three months later, the left tibia fracture model was again performed. The control and the treatment group (n = 24, per group, female). The treatment group was treated with an agonist (osthole). Detection of SMSCs in muscles and fracture healing at 7, 14, and 28 three time points (n = 8, 8, 8, female). To further clarify the scientific hypothesis, we innovatively used Pax7‐Cre^ERT2/+;β‐catenin^fx/fx transgenic mice (n = 12, per group, male). Knock out β‐catenin in SMSC to observe the proliferation and osteogenic differentiation of SMSCs, and OPF healing. In vitro primary cells of SMSCs from 3‐month‐old litter‐negative β‐catenin^fx/fx transgenic mice. After adenovirus‐CRE transfection, the myogenic and osteogenic differentiation of SMSC was observed.Results: We find that human SMSCs reduced proliferation and osteogenic differentiation in patients with OPF (−38.63%, P < 0.05). And through animal experiments, it was found that activation of β‐catenin promoted the proliferation and osteogenic differentiation of SMSC at the fracture site, thereby accelerating the healing of the fracture site (189.47%, P < 0.05). To prove this point of view, in the in vivo Pax7‐Cre^ERT2/+;β‐catenin^fx/fx transgenic mouse experiment, we innovatively found that knocking out β‐catenin in SMSC will cause a decrease in bone mass and bone microstructure, and accompanied by delayed fracture healing (−35.04%, P < 0.001). At the same time, through in vitro SMSC culture experiments, it was found that their myogenic (−66.89%, P < 0.01) and osteogenic differentiation (−16.5%, P < 0.05) ability decreased.Conclusions: These results provide the first practical evidence for a direct contribution of SMSCs to promote the healing of OPF with important clinical implications as it may help in the treatment of delayed healing and non‐union of OPFs, and mobilization of autologous stem cell therapy in orthopaedic applications.

Introduction: Osthole has a potential therapeutic application for anti-osteoporosis. The present study verified whether osthole downregulates osteoclastogenesis via targeting OPG. Methods: In vivo, 12-month-old male mice were utilized to evaluate the effect of osthole on bone mass. In vitro, bone marrow stem cells (BMSCs) were isolated and extracted from 3-month-old OPG^−/− mice and the littermates of OPG^+/+ mice. Calvaria osteoblasts were extracted from 3-day-old C57BL/6J mice or 3-day-old OPG^−/− mice and the littermates of OPG^+/+ mice. Results: Osthole significantly increased the gene and protein levels of OPG in primary BMSCs in a dose-dependent manner. The deletion of the OPG gene did not affect β-catenin expression. The deletion of the β-catenin gene inhibited OPG expression in BMSCs, indicating that osthole stimulates the expression of OPG via activation of β-catenin signaling. Conclusion: Osthole attenuates osteoclast formation by stimulating the activation of β-catenin-OPG signaling and could be a potential drug for the senile osteoporosis.

Osteoporosis is a systemic degenerative bone disease characterized by low bone mass and damage to bone microarchitecture, which increases bone fragility and susceptibility to fracture. The risk of osteoporosis increases with age; with the aging of the global population, osteoporosis is becoming more prevalent, adding to the societal healthcare burden. Histone modifications such as methylation, acetylation, ubiquitination, and ADP-ribosylation are closely related to the occurrence and development of osteoporosis. This article reviews recent studies on the role of histone modifications in osteoporosis. The existing evidence indicates that therapeutic targeting of these modifications to promote osteogenic differentiation and bone formation may be an effective treatment for this disease.