P035 - EXOGENOUS ADMINISTRATION OF IRISIN DURING CHRONIC TNBS-INDUCED GUT INFLAMMATION REVERSES INFLAMMATION-INDUCED ALTERATIONS IN BONE TURNOVER
(Room Poster Hall)
19 Jan 18
5:30 PM
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7:00 PM
Tracks:
Clinical and Research Challenges
A comorbidity of inflammatory bowel disease (IBD) is inflammation-induced bone loss characterized by elevated bone resorption and decreased bone formation. Fracture incidence is resultantly elevated. Using a TNBS rat model, we have found osteocytes, cells embedded in the bone matrix, have high TNF-α prevalence. Two proteins TNF-α regulates – RANKL, a driver of bone resorption, and sclerostin, an inhibitor of bone formation – were elevated concurrent with TNF-α. These alterations in osteocyte proteins correlated with changes in bone turnover. Irisin, a factor released during exercise, has been proposed to be a bone anabolic factor. We hypothesized exogenous irisin treatment during chronic IBD would exert anti-inflammatory actions improving IBD-associated bone outcomes. METHODS: 2-month old, male, Sprague Dawley rats instilled rectally with TNBS/Vehicle solutions for 4-weeks. 1-week after TNBS initiation, irisin-treated rats were given bi-weekly irisin injections. RESULTS: Proximal tibia cancellous bone had high osteoclast surface (OcS) and low bone formation rate (BFR) in TNBS, but treatment with irisin resulted in 2-fold higher BFR and 51% lower OcS vs. TNBS alone. TNBS rats had high distal femur cancellous osteocytes positive for TNF-α, but irisin lowered TNF-α+ osteocytes by 6.6-fold. Additionally, RANKL+ and sclerostin+ osteocytes were high in TNBS, but were 2- 4-fold lower in irisin-treated TNBS animals, no different from vehicle-treated rats. CONCLUSIONS: Chronic IBD results in alterations in bone turnover leading to bone loss. Irisin treatment reversed the high OcS and low BFR seen in animals with chronic gut inflammation. Osteocyte TNF-α and the factors it regulates (RANKL and sclerostin) were lowered to levels no different than vehicle-treated rats indicating irisin’s actions as an anti-inflammatory agent. Irisin is a potential novel therapeutic treatment for IBD and associated inflammatory comorbidities including inflammation-induced bone loss.