Gastrin For Prevention Of Steriod-associated Osteonecrosis In Rats

Objective: Steroid-associated osteonecrosis(SAON)is a common complication due to the wide clinical applications of steroid hormones.It usually involves the joints with heavy load-bearing,subsequent subchondral bone collapse and eventually artificial joint replacement.It is known as "undead cancer".Currently,effective strategy is to intervene in the differentiation of bone marrow stromal stem cells(BMSCs)at the early stage of osteonecrosis that are inhibiting osteoclast and adipocyte differentiation,and promoting osteogenic differentiation at necrotic siteand to subsequently prevent osteonerosis and progression effectively.Therefore,this study aims to investigate whether gastrin could play a crucial role in prevention of steroid-associated osteonecrosis in rats,and whether gastrin could directly inhibit the differentiation of osteoclasts,and promote bone mineralization and inhibit adipogenic effect in vitro.Methods: The rat model of SAON was established by combined injection that were lipopolysaccharide(600?g/kg)via the tail vein and methylprednisolone(50mg/kg)via intramuscular.It was divided into three groups: the non-treatment group,the low dosage group(300?g/kg)and the high dosage group(600?g/kg),and the drug was applied for two weeks.Based on the SAON model identification,we determined the efficacy of gastrin in SAON by osteoclast activity,mineralization and adipose formation ability.Meanwhile,the differentiation and proliferation of BMSCs were identified via in vitro study,and the osteogenesis and adipogenesis were also identified.In addition,the inhibitory effects of gastrin on the differentiation of bone marrow cells into osteoclasts.Results: In vivo results showed that gastrin could effectively prevent the occurrence and development of SAON in rats.In vitro experiments showed that gastrin could significantly inhibit the differentiation and maturation of osteoclasts and adipocytes,and significantly promote the differentiation of osteoblasts.Conclusion: This study presented for the first time that gastrin could significantly inhibit bone absorption by osteoclastogenic inhibition and promote bone formation by osteogenic induction,and subsequently could prevent steroid induced osteonecrosis in rats.It implies that there are important links between gastrointestinal hormones and bone metabolism diseases.