20(S)-Hydroxycholesterol (516-72-3) is an endogenous ligand for the LXR receptor.¹ It has anti-adipogenic and pro-osteogenic effects in mesenchymal stem cells mediated via a non-LXR dependent pathway.² The osteogenic effects of 20-(S)-hydroxycholesterol have been shown to be mediated by activation of hedgehog signaling and expression of genes associated with Notch signaling.³ Activation of Hedgehog is mediated via binding of 20(S)-hydroxycholesterol to Smoothened at a site distinct from the cyclopamine binding site.^4,5 It has also been found to be an endogenous ligand for the sigma 2 receptor.⁶

References/Citations:

1) Janowski et al. (1996), An oxysterol signaling pathway mediated by the nuclear receptor LXR7alpha; Nature, 383 728
2) Kha et al. (2004), Oxysterols regulate differentiation of mesenchymal stem cells: Pro-bone and Anti-fat: J. Bone Min. Res., 19 830
3) Kim et al. (2010), Osteogenic oxysterol, 20(S)-hydroxycholesterol, induces notch target gene expression in bone marrow stromal cells; J. Bone Miner. Res., 25 7823
4) Dwyer et al. (2007), Oxysterols are novel activators of the hedgehog signaling pathway in pluripotent mesenchymal cells; J. Biol. Chem., 282 8959
5) Nedelcu et al. (2013); Oxysterol binding to the extracellular domain of Smoothened in Hedgehog signaling; Nat. Chem. Biol., 9 557
6) Cheng et al. (2021); A proteome-wide map of 20(S)-hydroxycholesterol interactors in cell membranes; Nat. Chem. Biol., 17 1271