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. 2023 Apr 8;24(8):6935. doi: 10.3390/ijms24086935

Figure 2.

Figure 2

S1PR function in osteogenic cells. Schematic representation of the downstream signalling from S1PRs in osteoclast precursors (OCPs), osteoclasts (OCs), osteoblast precursors (OBPs), and osteoblasts (OBs). S1PRs are G-protein coupled receptors that activate various pathways and are present at different stages of OB and OC differentiation [17]. Within OCPs, S1PR1 and S1PR2 alter OC maturation via activation of Rho and Rac signalling pathways [24]. S1P can increase OCPs differentiation via Cox2, although the mechanism is not fully understood [24]. Although S1PR1-4 are expressed in OCs, the role of S1PR3 and S1PR4 are not currently understood [30]. S1PR1/2 can alter OC migration but the mechanisms underpinning this remain unclear. S1PR2 appears to be essential for OC activation. Within OBs, S1PR1 mediates OB differentiation via PI3K/AKT signalling and regulates migration via JAK/STAT signalling [31], resulting in chemoattraction in response to S1P [31], whereas S1PR2 increases OB differentiation via RhoA/ROCK/Smad signalling [30] and can also act through FAK/PI3K/AKT signalling to promote chemorepulsion. In OBs, S1PR1 increases OB proliferation [32] and survival via MAPK and PI3K signalling. S1PR1-3 are involved in mediating OB maturation through as of yet unknown signalling pathways. Activation of SphK1 in OBs promotes osteoblast maturation via autocrine S1P signalling through S1PR3 [23]. The function of S1PR4 in OBs is currently unknown. Created in Biorender.com.