Ostn-flox Mouse

Ostn, also known as Osteocrin, is a gene encoding a secreted myokine. It plays crucial roles in multiple biological processes. It binds to natriuretic peptide receptor 3 (NPR3), inhibits the degradation of natriuretic peptides, and enhances guanylyl cyclase-A (GC-A/NPR1) signaling [3]. It is involved in processes like bone growth, muscle homeostasis, and energy metabolism, and has implications in various diseases [1,2,3,4,5,6]. Genetic models, such as knockout (KO) mouse models, have been valuable in understanding its functions.

In skeletal muscle, RNA sequencing from wasting skeletal muscles of mice with heart failure showed reduced Ostn expression. Generating skeletal muscle-specific Ostn knockout and overexpressing mice demonstrated that reduced skeletal muscle Ostn levels exaggerate, while its overexpression attenuates cardiac dysfunction and myocardial fibrosis during pressure overload [1]. In adriamycin nephropathy, Ostn-transgenic mice and NPR3 knockout mice showed improvement in phenotypes like albuminuria and podocyte injuries, indicating Ostn works through NPR3. Conversely, Ostn KO mice had increased urinary albumin levels [3]. In the context of cardiac hypertrophy, the expression of Ostn was lower in Ang II-treated mouse heart. Overexpression of Ostn attenuated the hypertrophy and fibrosis of the heart in mice induced by Ang II [4]. For diabetic cardiomyopathy, Ostn expression was reduced in diabetic hearts, and its overexpression significantly attenuated cardiac injury and dysfunction in mice with streptozotocin treatment. OSTN silence aggravated cardiomyocyte apoptosis and injury upon hyperglycemic stimulation in vitro [6].

In conclusion, Ostn is essential in maintaining normal physiological functions in muscles, bones, heart, and kidneys. Studies using Ostn KO or overexpressing mouse models have revealed its significance in disease conditions such as heart failure, nephropathy, cardiac hypertrophy, and diabetic cardiomyopathy. These findings provide potential therapeutic targets for these diseases.