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Facilitation of human osteoblast apoptosis by sulindac and indomethacin under hypoxic injury.

Journal of cellular biochemistry (2011-09-02)
Cheng Liu, An-Ly Tsai, Yen-Chu Chen, Shih-Chen Fan, Chun-Hsien Huang, Chia-Ching Wu, Chih-Han Chang
ABSTRACT

Hypoxic-ischemia injury occurs after trauma causes consequential bone necrosis. Non-steroid anti-inflammatory drugs (NSAIDs) are frequently used in orthopedic clinics for pain relief. However, the underlying mechanism and outcome for usage of NSAIDs is poorly understood. To investigate the damage and loss of osteoblast function in hypoxia, two hypoxia mimetics, cobalt chloride (CoCl(2)) and desferrioxamine (DFO), were used to create an in vitro hypoxic microenvironment. The cell damage was observed by decreases of cell viability and increases in cyclooxygenase-2 and cleaved poly(ADP-ribose) polymerase (PARP). Cell apoptosis was confirmed by WST-1 cytotoxic assays and flow cytometry. The functional expression of osteoblast in alkaline phosphatase (ALP) activity was significantly decreased by CoCl(2) and inhibited when treated with DFO. To simulate the use of NSAID after hypoxic injury, four types of anti-inflammatory drugs, sulindac sulfide (SUL), indomethacin (IND), aspirin (Asp), and sodium salicylate (NaS), were applied to osteoblasts after 1 h of hypoxia mimetic treatment. SUL and IND further enhanced cell death after hypoxia. ALP activity was totally abolished in hypoxic osteoblasts under IND treatment. Facilitation of osteoblast apoptosis occurred regardless of IND dosage under hypoxic conditions. To investigate osteoblast in vivo, local hypoxia was created by fracture of tibia and then treated the injured mice with IND by oral feeding. IND-induced osteoblast apoptosis was confirmed by positive staining of TUNEL assay in fractured mice. Significant delay of fracture healing in bone tissue was also observed with the treatment of IND. These results provide information pertaining to choosing appropriate anti-inflammatory drugs for orthopedic patients.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Sodium salicylate, tested according to Ph. Eur.
Sigma-Aldrich
Sodium salicylate, puriss. p.a., ≥99.5% (NT)
Sigma-Aldrich
Sodium salicylate, puriss. p.a., reag. Ph. Eur., 99.5-101.0% (calc. to the dried substance)
Sigma-Aldrich
Sodium salicylate, ReagentPlus®, ≥99.5%
Sigma-Aldrich
Sodium salicylate, meets USP testing specifications