Osteoporosis, femoral head necrosis, and congenital bone defects are orthopedic disorders characterized by reduced bone generation and insufficient bone mass. Bone regenerative therapy primarily relies on the bone marrow mesenchymal stem cells (BMSCs) and their ability to differentiate osteogenically. Icariin (ICA) is the active ingredient of Herba epimedii, a common herb used in traditional Chinese medicine (TCM) formulations, and can effectively enhance BMSC proliferation and osteogenesis. However, the underlying mechanism of ICA action in BMSCs is not completely clear. In this review, we provide an overview of the studies on the role and mechanism of action of ICA in BMSCs, to provide greater insights into its potential clinical use in bone regeneration.

With increasing age, the microenvironment in the bone marrow is altered, leading to a decrease in bone marrow mesenchymal stem cell (BMSC) differentiation, which reduces the number of bone cells and weakens osteogenic capacity, resulting in osteoporosis (OP). The clinical manifestations of OP include bone loss, bone microstructural destruction and altered bone quality. Bone morphogenetic protein 2 (BMP2) serves an important role in inducing the osteogenic differentiation of mesenchymal stem cells (MSCs). Regulating the bone marrow matrix microenvironment and promoting osteogenic differentiation of BMSCs is of significance for both the prevention and treatment of OP. In the present study, isobaric tags for relative and absolute quantification (iTRAQ) high-throughput proteomics technology was combined with bioinformatics analysis to screen 249 differentially expressed proteins in human MSCs overexpressing BMP2, of which 173 were upregulated and 76 proteins were downregulated. The proteins were also involved in signaling pathways associated with extracellular matrix organization, osteoblast differentiation, ossification, bone development, chondrocyte differentiation and bone morphogenesis. By carefully screening the proteins, N-cadherin (CDH2), a protein with osteogenic differentiation potential, was verified by perturbations in the background of BMP2 overexpression. The role of CDH3 in the osteogenic differentiation of MSCs was confirmed by the regulation of several cognate osteogenic markers, suggesting CDH2 as a promising candidate in the field of osteogenesis.

Tau hyperphosphorylation is a typical pathological change in Alzheimer’s disease (AD) and is involved in the early onset and progression of AD. Epigenetic modification refers to heritable alterations in gene expression that are not caused by direct changes in the DNA sequence of the gene. Epigenetic modifications, such as noncoding RNA regulation, DNA methylation, and histone modification, can directly or indirectly affect the regulation of tau phosphorylation, thereby participating in AD development and progression. This review summarizes the current research progress on the mechanisms of epigenetic modification associated with tau phosphorylation.

The current treatment strategies for osteoporosis (OP) involve promoting osteogenic differentiation and inhibiting adipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). According to a theory of traditional Chinese medicine (TCM), the kidneys contain an “essence” that regulate bone metabolism and generate marrow. Kidney disorders are therefore considered to be a major cause of OP as per the principles of TCM, which recommends kidney-tonifying treatments for OP. The Zuogui pill (ZGP) is a classic kidney-tonifying medication that effectively improves OP symptoms. Studies have shown that ZGP can promote the osteogenic differentiation of BMSCs, providing scientific evidence for the TCM theory linking kidneys with bone metabolism. In this review, we have provided an overview of recent studies that examined the underlying mechanisms of ZGP mediated regulation of BMSC osteogenic and adipogenic differentiation.