Perspectives on Osteoarthritis Treatment with Mesenchymal Stem Cells and Radix Achyranthis Bidentatae

Abstract

Knee osteoarthritis, a widespread degenerative condition, impacts a younger population and leads to high disability rates. Nature often provides solutions for aging and disease prevention. Mesenchymal stem cells (MSCs) and Radix Achyranthis Bidentatae (AB) are natural substances with potential. MSCs can transform into various tissues, alleviating symptoms by releasing factors and miRNA, potentially slowing osteoarthritis progression. AB's compositions target knee joint cells, enhancing internal conditions and joint function. Both MSCs and AB share mechanisms for immune regulation, reducing cartilage apoptosis, promoting chondrocyte formation, and addressing osteoporosis. They also influence estrogen and gut flora. This article reviews their roles in treating osteoarthritis, discussing apoptosis reduction, chondrocyte growth, bone enhancement, angiogenesis, and regulation of estrogen and intestinal flora. It explores their relationship and suggests AB's potential in stimulating mesenchymal stem cell repair for knee osteoarthritis treatment.

Figure 1.

MSCs and AB reduce cartilage apoptosis through immunomodulation. In the treatment of knee osteoarthritis, exogenous stem cells have shown the effect of immunomodulation. Stem cells can secrete exosomes with multiple miRNAs that can reverse the imbalance of Th17/Treg, inhibit the secretion of inflammatory factors, weaken the NF-κB pathway, downregulate apoptotic genes, alleviate inflammation, and reduce chondrocyte apoptosis. AB also has immunomodulatory and anti-inflammatory effects in treating knee osteoarthritis. As a plant-derived drug, AB can potentially promote the secretion of exosomes that inhibit inflammation-related factors by acting on in situ stem cells.

Figure 2.

AB can potentially act on MSCs in situ to promote the differentiation into chondrocytes and the secretion of MSC-exosomes to further achieve chondrocyte proliferation. Exogenous stem cells can differentiate into cartilage and activate signaling pathways such as Wnt5a/b-catenin, PI3K-PDK-AKT, and IKK/NF-κB to improve chondrogenesis. In addition, the exosomes from these cells carry various miRNAs, such as miR-205-5p, miR-381-3p, miR-29a, and miR-29b, which can promote the process of the differentiation process of in situ stem cells into chondrocytes and contribute to chondrocyte proliferation. AB can improve the proliferation of chondrocytes in knee osteoarthritis patients and affect the cell cycle. AB can potentially act on in situ MSCs to improve the differentiation into chondrocytes and increase the secretion of MSC-exosomes to further enhance chondrocyte proliferation.

Figure 3.

Both MSCs and AB can balance osteoclasts and osteoblasts, promote bone formation, and inhibit bone resorption, thereby improving osteoporosis of subchondral bone. AB can potentially achieve anti-osteoporosis by stimulating in situ stem cells. MSCs can differentiate into bone, and the injection of MSCs can effectively supplement the amount of MSCs and promote bone formation to treat osteoporosis. Osteoporosis is the result of an imbalance in the number of osteoblasts and osteoclasts, which is closely linked to osteogenic differentiation (OD). Stem cells can activate Wnt/β-catenin and BMP2/SMAD1 signaling pathways to regulate osteogenic differentiation and inhibit RANKL and other signaling pathways to suppress osteoclast formation and bone resorption. Moreover, miRNAs such as miRNA-140e5p in MSC-exosomes can upregulate BMP2 and promote MSCs’ osteogenic differentiation, thereby alleviating the development of osteoporosis. Stem cells can also inhibit the secretion of inflammatory factors such as IL-1a, IL-1b, IL-18, and TNF-α, to avoid bone loss. Both AB and MSCs have the effect of balancing osteoclasts and osteoblasts, promoting bone formation and inhibiting bone resorption, thus improving osteoporosis. AB can potentially achieve anti-osteoporosis by activating the above functions of in situ stem cells.

Figure 4.

Both AB and MSCs have the effect of promoting the proliferation of endothelial cells and preventing thrombosis, thereby improving the microcirculation around the knee joint. AB can potentially achieve this by stimulating the in situ stem cells. Stem cells have the potential for vascular epithelial differentiation, and MSCs’ exosomes can promote in situ vascular epithelial cell differentiation and repair vascular damage. MSCs can increase endothelial cell proliferation, migration and vessel formation through LncRNA-H19, miR-130a, miR-146a, mi -199b-3p, and mi-125a-5p. MSC-exosomes can activate the signaling pathways such as p53-Notch, PI3K/AKT, MAPK, and JAK/STAT6, to achieve angiogenesis. MSCs are capable of immunomodulation, improving the microenvironment, and lowering the levels of CRP, pro-inflammatory cytokines and NETs, which helps reduce thrombosis formation caused by NETs. AB and MSCs both have the effect of promoting the proliferation of endothelial cells and preventing thrombosis, so as to improve the microcirculation around the knee joint in the treatment of osteoarthritis. AB can potentially achieve this by promoting the secretion of relevant exosomes through the activation of in situ stem cells.

Figure 5.

Both MSCs and AB have the effect of improving ovarian function and promoting estrogen secretion. AB can potentially affect in situ stem cells around the ovary to promote ovarian function and increase estrogen secretion. Stem cells can promote follicular development, increase local ovarian vascularization, enhance follicle and mesenchymal cell proliferation, reduce cell apoptosis and follicular atresia. They can also improve mitochondrial quality, increase mitochondrial DNA replication, reduce oxidative damage, and cell apoptosis, and increase the quantity and quality of ovulated mature oocytes. MiR-21 and miR-644-5p in MSC-exosomes can inhibit the apoptosis of ovarian granule cells and restore the ovarian function. MSCs also inhibit apoptosis of follicular cells through the PI3K/AKT and AGE-RAGE signaling pathways. AB and MSCs can improve ovarian function and promote estrogen secretion. AB can potentially activate the in situ stem cells around the ovary to promote ovarian function and avoid the reduction of serum estradiol (E2).

Figure 6.

Both MSCs and AB have the function of maintaining the balance of intestinal flora. AB can possibly activate the MSCs in the intestine to regulate the intestinal flora. Oral administration of stem cell-loaded hydrogel microcapsules can improve the disorders of specific bacterial genera, including Bacteroides acidifaciens, Lactobacillus (L.) gasseri, Lactobacillus reuteri, and L. intestinalis. This improvement optimizes microbial composition and abundance. Oral administration of AB supplements can reduce Escherichia coli, Salmonella, and Staphylococcus aureus in feces; the increasing number of lactobacillus and bifidobacteria can maintain the microbiome balance between the intestinal microbiota and the body. Both MSCs and AB have the function of maintaining the balance of intestinal flora. AB can potentially activate the MSCs in the intestine and promote the secretion of MSC-exosomes to affect the intestinal flora.

Figure 7.

MSCs and AB have efficacy in treating knee osteoarthritis in six aspects. There are six similar functions of MSCs and AB in the treatment of osteoarthritis: 1. reduce the cartilage apoptosis through immunomodulation; 2. promote chondrocyte proliferation; 3. improve subchondral bone microenvironment to achieve anti-osteoporosis; 4. promote angiogenesis and improve microcirculation to achieve anti-thrombosis; 5. promote the follicular cells activity to increase the estrogen secretion; 6. optimize intestinal flora. Because of the similar mechanism between MSCs and AB in the treatment of knee osteoarthritis, AB possibly achieves the above effects by activating the body’s in situ cells. The joint application of AB and stem cells can potentially produce a greater therapeutic effect on knee osteoarthritis.