Icariin promotes the repair of bone marrow mesenchymal stem cells in rabbit knee cartilage defects via the BMP/Smad pathway

Abstract

Background: Icariin (ICA) has been widely used in the treatment of osteoporosis. However, the potential mechanism of its critical role in repairing knee cartilage damage still needs to be further clarified.Methods: First, rabbit bone marrow mesenchymal stem cells (BMSCs) were isolated, cultured, and identified. Subsequently, BMSCs were treated with different concentrations of ICA. Cell Counting Kit 8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) were used to evaluate the cell proliferation in each group. Alcian Blue staining, immunofluorescence, and western blotting were used to evaluate the ability of BMSCs to differentiate cartilage. In addition, a rabbit knee cartilage injury model was established.Evaluation of cartilage defects in each group was performed according to the classification system outlined by the International Cartilage Repair Society (ICRS). Hematoxylin and eosin (HE), Alcian Blue, and immunohistochemistry were used to analyze the pathological status of knee cartilage. Results:In vitro, the results showed that ICA promoted the cartilage differentiation of BMSCs as well as cell proliferation. In addition, ICA promoted the expression of type II collagen (COL2A1), aggrecan, and bone morphogenetic protein 2 (BMP2) in BMSCs, while BMP-Smad inhibitor (Noggin) reversed the repair effect of ICA on BMSCs. In vivo, our results showed that the ICRS score of the BMSC and ICA treatment group was higher. Moreover, BMSC and ICA treatment promoted the proliferation of chondrocytes and repaired the cartilage-like tissue on the surface of cartilage defect. Conclusions:The combined application of ICA and BMSCs can repair rabbit knee cartilage injury by regulating the BMP/Smads pathway, indicating that ICA and BMSCs may be a viable clinical treatment strategy for knee cartilage damage.

Advancements in tissue engineering for articular cartilage regeneration

“…Hypoxia-treated Exos have been found to enhance the proliferation, migration, anabolism, and anti-inflammatory effects of chondrocytes more effectively than Exos under normal oxygen conditions [ 73 ]. Icariin has shown promise in accelerating cartilage ECM synthesis, inhibiting degradation, and promoting cartilage-specific gene expression and differentiation [ [92] , [93] , [94] ]. The mechanism is related to the increase in aggregation protein, BMP2, and COL2A1 in BMSCs [ 95 ] and the activation of the Wnt/s-catenin signaling pathway [ 96 ].…”

“…Another study by Yang et al [ 75 ] loaded BMSCs onto gelatin methacryloyl hydrogel microspheres with superwetting properties, enabling sustained release of TGF-β and promoting cartilage regeneration at bone defect sites. By manipulating factors such as carrier material properties, degradation rates, and cross-linking mechanisms, desired release kinetics can be achieved [ 94 , 173 ]. This approach ensures sustained and localized delivery of therapeutic agents, enhancing their biological activity and facilitating targeted cartilage regeneration.…”

Engineered biochemical cues of regenerative biomaterials to enhance endogenous stem/progenitor cells (ESPCs)-mediated articular cartilage repair

“… [ 22 ] Icariin N/A in vivo ; rabbit model Icariin promoted proliferation and chondrogenic differentiation of BM-MSCs in vitro and rabbit knee AC repair via the BMP/Smad pathway. [ 114 ] Gene targeting factors and EVs antimiR-221 fibrin/HA ex vivo ; bovine OC explant Hydrogel loaded with antimiR-221/lipofectamine could drastically enhance AC regeneration through ESPCs. [ 24 ] miR-29b-5p (SKPPGTSS) SAP hydrogel in vivo ; mice model Sustained hydrogel-based delivery of miR-29b-5p could promote the recruitment and subsequent chondrogenic differentiation of endogenous cells, which were crucial for successful AC repair and chondrocyte rejuvenation.…”

A mechanistic review of chinese medicine polyphenols on bone formation and resorption

“…In addition, up-regulating the expression of Mir-335–5p and inhibiting phosphatase and tensin homolog deleted on chromosome ten (PTEN) can improve the susceptibility of osteoporosis (OP), thus providing new strategies for the prevention and treatment of OP ( Teng et al, 2022 ). ICA can promote osteogenic differentiation by regulating the BMP/Smads pathway, the BMA1-BMP2 signaling pathway, and the BMP-2/Smad 5/Runx two and WNT/β-catenin pathways in BMSCs ( Gao et al, 2021 ; Zhang et al, 2021 ; Jiao et al, 2022 ). Epimedium promotes the migration of bone marrow mesenchymal stem cells in vitro and in vivo through the MAPK signaling pathway ( Jiao et al, 2018 ).…”