Extracellular IL-37 promotes osteogenic differentiation of human bone marrow mesenchymal stem cells via activation of the PI3K/AKT signaling pathway

Abstract

Interleukin (IL)-37, a pivotal anti-inflammatory cytokine and a fundamental inhibitor of innate immunity, has recently been shown to be abnormally expressed in several autoimmune-related orthopedic diseases, including rheumatoid arthritis, ankylosing spondylitis, and osteoporosis. However, the role of IL-37 during osteogenic differentiation of mesenchymal stem cells (MSCs) remains largely unknown. In this study, extracellular IL-37 significantly increased osteoblast-specific gene expression, the number of mineral deposits, and alkaline phosphatase activity of MSCs. Moreover, a signaling pathway was activated in the presence of IL-37. The enhanced osteogenic differentiation of MSCs due to supplementation of IL-37 was partially rescued by the presence of a PI3K/AKT signaling inhibitor. Using a rat calvarial bone defect model, IL-37 significantly improved bone healing. Collectively, these findings indicate that extracellular IL-37 enhanced osteogenesis of MSCs, at least in part by activation of the PI3K/AKT signaling pathway.

A novel lncRNA LNC_000052 leads to the dysfunction of osteoporotic BMSCs via the miR-96-5p–PIK3R1 axis

“…Meanwhile, LNC_000052 expression was positively associated with Icam1, a gene which inhibits osteogenesis 19 , and Medag, a gene which promotes adipogenesis 20 , indicating that LNC_000052 might affect BMSC differentiation. In the present study, LNC_000052 overexpression led to reductions in the viability, migration, and differentiation properties of BMSCs, which were consistent with PI3K-AKT pathway dysfunction 21 . Notably, the negative regulatory subunit of PI3K, PIK3R1, was predicted to be a positively co-expressed mRNA of LNC_000052.…”

Low-Dose IL-34 Has No Effect on Osteoclastogenesis But Promotes Osteogenesis of Hbmscs Partly Via Activation of The PI3K/AKT And ERK Signaling Pathways 

“…Several studies have emphasized the key role of the PI3K/AKT signaling pathway for all of the periods of osteogenic differentiation, maturation, and bone formation [38][39][40][41]. Not only chondrocyte differentiation would be impaired, but also longitudinal bone growth would be inhibited by blocking the PI3K/AKT signaling pathway [3,42]. With the activation of the PI3K/AKT signaling pathway, IL-34 switched the phenotype of Kupffer cells from M1 to M2 in vitro [43].…”

“…Bone defects or fracture nonunion, which is still no e cacious way for the treatment, being one of the most intractable clinical diseases for orthopedic surgeons [1,2]. Severe fracture, bone tumor ablation, debridement of a wide range of bone infections and congenital defects can lead to the failure of fracture healing [3]. Fracture healing is known as an intricate physiologic process that the vascularity at fracture site, mechanical environment, growth factors, scaffolds and mesenchymal stem cells (MSCs) coordinate spatially and temporally to work towards restoring bone structural integrity without scar formation [4,5].…”

“…Meanwhile, many cytokines and growth factors can affect the differentiation of BMSCs and improve the migration and homing of BMSCs for bone regeneration [30][31][32]. Recently, several studies noted that an in ammatory microenvironment can potentially increase the immunogenicity of BMSCs and decrease BMSCs viability and differentiation capacity [3,8,31].…”

WITHDRAWN: Elucidating the mechanisms of Tibetan medicine Ershiwuwei Lvxue Pill in the treatment of rheumatoid arthritis via a system pharmacological approach

“…Studies have suggested that the PI3K/Akt signaling pathway contributes to excessive cell proliferation, migration, and invasion in RA-FLSs [88,89]. Bone marrow MSCs (BMSCs), play a key role in the healing of bone defects, has been applied for the treatment of RA via activation of the PI3K/AKT signaling pathway [90].…”