Changes in Musculoskeletal System and Metabolism in Osteoporotic Rats Treated With Urocortin.

Dominik Saul,Laura Katharina Geisberg,Mohammad Tezval,Torben Gehle,Stephan Sehmisch,Marina Komrakova,Daniel Bernd Hoffmann

doi:10.3389/fendo.2019.00400

Dominik Saul, Laura Katharina Geisberg + Show 5 more

Open Access

https://doi.org/10.3389/fendo.2019.00400

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Abstract

Objective: In aging population, postmenopausal osteoporosis and decline of musculoskeletal function, referred to as “frailty syndrome” lead to loss of bone and muscle, causing falls, and fall-related injuries. To limit the impact of this portentous duo, simultaneous treatment of both is needed. Urocortin (UCN) has been reported to improve osteoporotic bone properties while its effect on muscle has not been addressed yet.Design and Methods: We aimed to investigate the effect of urocortin in vivo on skeletal muscle structure in osteopenic rats. Sixty Sprague-Dawley rats were divided into five groups: four were ovariectomized (OVX) and one underwent sham operation (SHAM). One ovariectomized group was left untreated (OVX), while one was treated with urocortin s.c. in 3 μg/kg body weight (bw) (OVX+UCN low), one with 30 μg/kg (OVX+UCN high), while one group was treated with estradiol orally (OVX+E: 0.2 mg/kg bw), each for 35 days. Mm. gastrocnemius, longissimus, and soleus were isolated and capillary density as well as diameters of type I and II fibers were measured. In addition, we examined the effect of UCN on tibia using biomechanical, micro-CT and ashing analysis and investigated the blood serum.Results: We demonstrated a positive effect of UCN on M. soleus, in which fiber diameter was positively influenced. The biomechanical and structural parameters of bone were not changed in UCN treated rats. The higher cholesterol, glucose and triglyceride levels in the “UCN high” group raise concern about this treatment.Conclusions: Our results portray urocortin as a substance that can be assessed for future therapeutic treatments of estrogen deficiency.New and Noteworthy: Urocortin has a positive effect on M. soleus (diameter). Urocortin raises serum cholesterol and triglyceride levels. Bone tissue was not affected by UCN.

Highlights

Due to the high prevalence of postmenopausal osteoporosis [1, 2], a strong muscular function is essential for the protection of the incorporated bone and physical coordination to prevent falls
We demonstrated a positive effect of UCN on M. soleus, in which fiber diameter was positively influenced
Our results portray urocortin as a substance that can be assessed for future therapeutic treatments of estrogen deficiency

Summary

Introduction

Due to the high prevalence of postmenopausal osteoporosis [1, 2], a strong muscular function is essential for the protection of the incorporated bone and physical coordination to prevent falls. In recent decades and with a distinct diagnostic definition, multiple therapeutic options and breakthroughs have been developed for osteoporosis [8, 9], whereas muscle-related research has not proceeded as far [10, 11]. Post-menopausal estrogen replacement therapy (ERT) was often recommended for prevention and treatment of osteoporosis [12] as well as for maintaining muscle strength and mass [13, 14]. The effect of vitamin D supplementation remains inconclusive, beneficial effects on muscle strength and prevention of falls in sarcopenic post-menopausal women have been reported [21]. Creatine supplementation has been proposed to positively affect sarcopenic state in aging postmenopausal women, while effect on bone remains inconclusive [22]

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