Oxysterols enhance osteoblast differentiation in vitro and bone healing in vivo

摘要: Oxysterols, naturally occurring cholesterol oxidation products, can induce osteoblast differentiation. Here, we investigated short-term 22(S)-hydroxycholesterol + 20(S)-hydroxycholesterol (SS) exposure on osteoblastic differentiation of marrow stromal cells. We further explored oxysterol ability to promote bone healing in vivo. Osteogenic was assessed by alkaline phosphatase (ALP) activity, osteocalcin (OCN) mRNA expression, mineralization, and Runx2 DNA binding activity. To explore the effects osteogenic oxysterols vivo, utilized critical-sized rat calvarial defect model. Poly(lactic-co-glycolic acid) (PLGA) scaffolds alone or coated with 140 ng (low dose) 1400 (high cocktail were implanted into defects. Rats sacrificed at 6 weeks examined three-dimensional (3D) microcomputed tomography (microCT). Bone volume (BV), total (TV), BV/TV ratio measured. Culture SS for 10 min significantly increased ALP activity after 4 days, while 2 h mineralization 14 days. Four-hour treatment OCN measured 8 days nuclear protein an OSE2 site The defects showed slight control group. However, adsorbed low high-dose enhanced formation. Histologic examination confirmed formation sites grafted oxysterol-adsorbed scaffolds, compared mostly fibrous tissue sites. Our results suggest that brief triggered events leading cell function vitro These identify as potential agents local systemic enhancement