Loss of Ovarian Function Results in Increased Loss of Skeletal Muscle in Arthritic Rats

Abstract

Objective We studied the effects of loss of ovarian function (ovariectomy) on muscle mass of gastrocnemius and the mRNA levels of IGF-1, atrogin-1, MuRF-1, and myostatin in an experimental model of rheumatoid arthritis in rats. Methods We randomly allocated 24 female Wistar rats (9 weeks, 195.3 AE 17.4 grams) into four groups: control (CT-Sham; n ¼ 6); rheumatoid arthritis (RA; n ¼ 6); ovariectomy without rheumatoid arthritis (OV; n ¼ 6); ovariectomy with rheumatoid arthritis (RAOV; n ¼ 6). We performed the ovariectomy (OV and RAOV) or Sham (CTSham or RA) procedures at the same time, fifteen days before the rheumatoid arthritis induction. The RA and RAOV groups were immunized and then were injected with Met-BSA in the tibiotarsal joint. After 15 days of intra-articular injections the animals were euthanized. We evaluated the external manifestations of rheumatoid arthritis (perimeter joint) as well as animal weight, and food intake throughout the study. We also analyzed the cross-sectional areas (CSA) of gastrocnemius muscle fibers in 200 fibers (H&E method). In the gastrocnemius muscle, we analyzed mRNA expression by quantitative real time PCR followed by the Livak method (ΔΔCT). Results The rheumatoid arthritis induced reduction in CSA of gastrocnemius muscle fibers. The RAOV group showed a lower CSA of gastrocnemius muscle fibers compared to RA and CT-Sham groups. Skeletal muscle IGF-1 mRNA increased in arthritics and ovariectomized rats. The increased IGF-1 mRNA was higher in OV groups than in the RA and RAOV groups. Antrogin-1 mRNA also increased in the gastrocnemius muscle of arthritic and ovariectomized rats. However, the increased atrogin-1 mRNA was higher in RAOV groups than in the RA and OV groups. Gastrocnemius muscle MuRF-1 mRNA increased in the OV and RAOV groups, but not in the RA and Sham groups. However, the

Aerobic exercise attenuates the effects of ovariectomy and sedentarism on body composition and food intake in female rats

“…In the 23 rd week of life, the rats were submitted to Ovariectomy (OVX) or laparotomy (Sham) surgery. The animals were previously anesthetized with intramuscular ketamine (70mg/kg) and intramuscular xylazine (8mg/kg), receiving subcutaneous administration of the anti-inflammatory substance Ketofen: 2mg/kg/3d and antibiotic (sodium ampicillin: 30mg/kg) kg/5d) [20,21]. After 3 weeks of recovery, the animals were allocated into 4 groups (n=10), in a 2x2 factorial design: SHAM Sedentary (SS), SHAM Exercised (SE), OVX Sedentary (OS) e OVX Exercised (OE).…”

Acute resistance exercise reduces increased gene expression in muscle atrophy of ovariectomised arthritic rats

“…Arthritic rats (RA and RAOV) showed reduction in fibres CSA of gastrocnemius muscle when compared to rats without arthritis (CT-Sham). Indeed, rheumatoid arthritis-induced LSM has been consistently demonstrated in animal [ 5 , 13 , 25 ] and human studies [ 27 ]. Additionally, we observed that the rheumatoid arthritis induced a substantial increase in the atrogin-1 gene expression in skeletal muscle.…”

“…Fifteen days after intra-articular injection, the RAEX and RAOVEX groups performed an acute RE session and after six hours of the end of workout were euthanised at the same time of day and time. The gastrocnemius muscle of the left hind paw was removed, weighed, cleaned, and their white portion was obtained and stored in TRIzol at –80°C for molecular analysis [ 13 ]. We investigated the gastrocnemius white portion because it possesses more fast-twitch fibres [ 12 , 21 ].…”

“…Notably, loss of ovarian function (LOF), such as menopause or ovariectomy, has been reported to be a direct contributor to LSM and also through interactions with inflammation [ 9 – 12 ]. We have shown that LOF results in increased RA-induced LSM associated with increased ubiquitin ligases atrogin-1 and MuRF-1 in arthritic rats [ 13 ]. Thus, since women naturally progress to menopause or can be subjected to ovariectomy, the identification of interventions against RA-induced LSM is necessary for women with loss of ovarian function.…”