title: Inflammatory Bowel Disease in a Rodent Model Alters Osteocyte Protein Levels Controlling Bone Turnover.
abstract: Bone loss is a common comorbidity of inflammatory bowel disease (IBD), leading to elevated fracture risk in these patients. Inflammatory factors associated with IBD cause increased bone resorption and decreased bone formation with multiple factors implicated as instigators of these alterations. In this project, we examined the influence of IBD on osteocyte proteins in male rats (2 months old) divided into two groups: induced gut inflammation via 2,4,6-trinitrobenzenesulfonic acid (TNBS) enema, and vehicle control. We examined the prevalence of two pro-inflammatory cytokines, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), an anti-inflammatory cytokine, interleukin-10 (IL-10), the anabolic factor insulin-like growth factor-I (IGF-I), osteoclastogenesis regulators RANKL and OPG, and the bone formation inhibitor sclerostin in osteocytes in three bone compartments 4 weeks after initiation of gut inflammation. Histomorphometry of the proximal tibia and fourth lumbar vertebra revealed lower bone volume, lower bone formation rate (BFR), lower osteoid surface (OS), and higher osteoclast surface (Oc.S) with TNBS. Tibial mid-shaft periosteal BFR was also lower with TNBS. Immunohistochemical staining of the distal femur demonstrated that %TNF-α+, %IL-6+, %RANKL+, and %OPG+osteocytes were elevated in cancellous bone in TNBS animals compared to vehicle. These changes were coincident with increased bone resorption. With regression analysis, %RANKL+osteocytes statistically predicted the increase in cancellous Oc.S (R2= 0.565). Increased %sclerostin+osteocytes observed in the TNBS treatment predicted declines in cancellous OS (R2= 0.581) as well as BFR in cancellous and cortical bone (R2= 0.674, R2= 0.908, respectively). Contrary to our hypothesis, %IGF-I+osteocytes increased in TNBS animals. In conclusion, the IBD model produced a systemic inflammation that altered the regulatory protein profile in osteocytes that control bone resorption and bone formation, likely contributing to IBD-induced bone loss. These data highlight a potential mechanistic role of osteocytes in inflammatory bone loss associated with IBD and systemic inflammation. © 2017 American Society for Bone and Mineral Research.
authors: Department of Health and Kinesiology, Texas A&M University Health Science Center, College Station, TX, USA.
authors: Corinne E
authors: CE
authors: Metzger
authors: Department of Medical Physiology, College of Medicine, Texas A&M University, College Station, TX, USA.
authors: Anand
authors: A
authors: Narayanan
authors: Department of Medical Physiology, College of Medicine, Texas A&M University, College Station, TX, USA.
authors: David C
authors: DC
authors: Zawieja
authors: Department of Health and Kinesiology, Texas A&M University Health Science Center, College Station, TX, USA.|Graduate Faculty of Nutrition, Texas A&M University, College Station, TX, USA.
authors: Susan A
authors: SA
authors: Bloomfield
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D016723:Bone Remodeling; D000071556:Cancellous Bone / Q000378:metabolism* / Q000473:pathology; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D005819:Genetic Markers; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D008297:Male; D010011:Osteocytes / Q000378:metabolism* / Q000473:pathology; D053244:Osteoprotegerin / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013977:Tibia / Q000378:metabolism* / Q000473:pathology; D014302:Trinitrobenzenesulfonic Acid / Q000633:toxicity
chemical_list: D019485:Bone Morphogenetic Proteins; D016207:Cytokines; D005819:Genetic Markers; D053244:Osteoprotegerin; C486031:Sost protein, rat; C506032:Tnfrsf11b protein, rat; D014302:Trinitrobenzenesulfonic Acid
keywords: BONE HISTOMORPHOMETRY; CYTOKINES; GROWTH HORMONE/IGF-I; OSTEOIMMUNOLOGY