OSM is overexpressed in knee osteoarthritis and Notch signaling is involved in the effects of OSM on MC3T3-E1 cell proliferation and differentiation

Abstract

Abstract. Knee osteoarthritis (OA) is the most prevalent type of OA and the cytokine, oncostatin M (OSM), may contribute to the pathogenesis of OA. However, the exact role of OSM in the development of knee OA and the underlying mechanisms are not yet fully understood. This study was designed to detect the expression of OSM in the synovial tissue of patients with knee OA. Furthermore, we investigated whether Notch signaling is involved in the effects of OSM on MC3T3-E1 cell proliferation and differentiation. The synovial tissue of the knee joint was collected from 32 patients with knee OA. We detected OSM mRNA and protein expression (by RT-qPCR and western blot analysis, respectively) in the synovial tissue of the knee joint, and the expression level of OSM was higher in the patients with knee OA compared with the controls. MTT assay was used in the in vitro experiments to determine MC3T3-E1 cell proliferation, and cell differentiation was determined by measuring alkaline phosphatase (ALP) activity and osteocalcin (OCN) expression. The results from our in vitro experiments revealed that OSM induced bone formation by increasing osteoblast cell proliferation and differentiation. In addition, the expression levels of Notch ligand, receptor and target gene, including Delta-like 1 (Dll1), Notch homolog 1 (Notch1) and Hes family bHLH transcription factor 1 (Hes1) were decreased following treatment with OSM in a time-dependent manner in the MC3T3-E1 cells. A Dll1 overexpression vector was transfected into the cells to activate Notch signaling, and the results revealed that the activation of Notch signaling attenuated the effects of OSM on MC3T3-E1 cell proliferation and differentiation. In conclusion, our data demonstrate that elevated levels of OSM in synovial tissue induce bone formation by increasing osteoblast cell proliferation and differentiation. The Notch signaling pathway was found to be one of the signaling pathways that inhibit OSM-induced MC3T3-E1 cell proliferation and differentiation. The findings of this study may broaden our understanding of the mechanisms behing the role of OSM in the development of knee OA.

Increased Activity of the Chondrocyte Translational Apparatus Accompanies Osteoarthritic Changes in Human and Rodent Knee Cartilage

“…We next investigated whether inclusion of an additional cytokine would have either a cumulative effect or a synergetic effect on protein synthesis. We chose the cytokine OSM, because its expression is elevated in OA cartilage and it also stimulates the STAT‐3 pathway (as shown in Supplementary Figure 3C, http://onlinelibrary.wiley.com/doi/10.1002/art.39947/abstract) . Akt (Ser 473 ) phosphorylation was more robust when chondrocytes were treated with both cytokines than upon treatment with IL‐1β alone (Figure C).…”

Tougu Xiaotong capsule exerts a therapeutic effect on knee osteoarthritis by regulating subchondral bone remodeling

“…ALP is essential for bone mineralization, which is secreted by osteoblast (34). Increased ALP level in serum has been observed in conditions such as rapid bone loss (35) and fracture risk (36,37). TRAP is secreted by osteoclasts during bone resorption, and serum TRAP activity correlates with resorptive activity in disorders of bone metabolism (14).…”

A Role for Soluble IL-6 Receptor in Osteoarthritis

“…In particular, OSM, in concert with TNF-α and IL-1β, have been implicated in the inflammatory process associated with OA wherein OSM mediated the degradation of aggrecan and hyaluronan, and where aggrecan degradation was associated with an increase in the low molecular weight G3 product of aggrecan [ 42 ]. Furthermore, Ni et al [ 43 ] suggested that OSM may be involved in altering the metabolism of bone associated with OA progression. In addition, Greene and Loesser [ 44 ] showed that the chondrocyte in response to OSM and IL-1β, as well as growth factors such as IGF-1, may be responsible for initiating “cross-talk” between PI3K-Akt, MAP kinase, and the JAK-STAT pathways, which could provide the mechanism in OA for the differential responsiveness between anabolic and catabolic pathways in response to these factors.…”