A pilot study: effect of irisin on trabecular bone in a streptozotocin-induced animal model of type 1 diabetic osteopathy utilizing a micro-CT

Background Osteoporosis is a significant co-morbidity of type 1 diabetes mellitus (DM1) leading to increased fracture risk. Exercise-induced hormone ‘irisin’ in low dosage has been shown to have a beneficial effect on bone metabolism by increasing osteoblast differentiation and reducing osteoclast m...

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Main Authors: Sahar Mohsin, Fiona Brock, Suneesh Kaimala, Charlene Greenwood, Mohsin Sulaiman, Keith Rogers, Ernest Adeghate
Format: Article
Language:English
Published: PeerJ Inc. 2023-10-01
Series:PeerJ
Subjects:
Online Access:https://peerj.com/articles/16278.pdf
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author Sahar Mohsin
Fiona Brock
Suneesh Kaimala
Charlene Greenwood
Mohsin Sulaiman
Keith Rogers
Ernest Adeghate
author_facet Sahar Mohsin
Fiona Brock
Suneesh Kaimala
Charlene Greenwood
Mohsin Sulaiman
Keith Rogers
Ernest Adeghate
author_sort Sahar Mohsin
collection DOAJ
description Background Osteoporosis is a significant co-morbidity of type 1 diabetes mellitus (DM1) leading to increased fracture risk. Exercise-induced hormone ‘irisin’ in low dosage has been shown to have a beneficial effect on bone metabolism by increasing osteoblast differentiation and reducing osteoclast maturation, and inhibiting apoptosis and inflammation. We investigated the role of irisin in treating diabetic osteopathy by observing its effect on trabecular bone. Methods DM1 was induced by intraperitoneal injection of streptozotocin 60 mg/kg body weight. Irisin in low dosage (5 µg twice a week for 6 weeks I/P) was injected into half of the control and 4-week diabetic male Wistar rats. Animals were sacrificed six months after induction of diabetes. The trabecular bone in the femoral head and neck was analyzed using a micro-CT technique. Bone turnover markers were measured using ELISA, Western blot, and RT-PCR techniques. Results It was found that DM1 deteriorates the trabecular bone microstructure by increasing trabecular separation (Tb-Sp) and decreasing trabecular thickness (Tb-Th), bone volume fraction (BV/TV), and bone mineral density (BMD). Irisin treatment positively affects bone quality by increasing trabecular number p < 0.05 and improves the BMD, Tb-Sp, and BV/TV by 21–28%. The deterioration in bone microarchitecture is mainly attributed to decreased bone formation observed as low osteocalcin and high sclerostin levels in diabetic bone samples p < 0.001. The irisin treatment significantly suppressed the serum and bone sclerostin levels p < 0.001, increased the serum CTX1 levels p < 0.05, and also showed non-significant improvement in osteocalcin levels. Conclusions This is the first pilot study to our knowledge that shows that a low dose of irisin marginally improves the trabecular bone in DM1 and is an effective peptide in reducing sclerostin levels.
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spelling doaj.art-ade66565d15d492aafba0b682052df072023-12-03T10:44:32ZengPeerJ Inc.PeerJ2167-83592023-10-0111e1627810.7717/peerj.16278A pilot study: effect of irisin on trabecular bone in a streptozotocin-induced animal model of type 1 diabetic osteopathy utilizing a micro-CTSahar Mohsin0Fiona Brock1Suneesh Kaimala2Charlene Greenwood3Mohsin Sulaiman4Keith Rogers5Ernest Adeghate6Department of Anatomy, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, Abudhabi, United Arab EmiratesCranfield Forensic Institute, Cranfield University, Shrivenham, United KingdomDepartment of Anatomy, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, Abudhabi, United Arab EmiratesSchool of Chemical and Physical Sciences, Keele University, Newcastle-under-Lyme, Staffordshire, United KingdomDepartment of Anatomy, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, Abudhabi, United Arab EmiratesCranfield Forensic Institute, Cranfield University, Shrivenham, United KingdomDepartment of Anatomy, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, Abudhabi, United Arab EmiratesBackground Osteoporosis is a significant co-morbidity of type 1 diabetes mellitus (DM1) leading to increased fracture risk. Exercise-induced hormone ‘irisin’ in low dosage has been shown to have a beneficial effect on bone metabolism by increasing osteoblast differentiation and reducing osteoclast maturation, and inhibiting apoptosis and inflammation. We investigated the role of irisin in treating diabetic osteopathy by observing its effect on trabecular bone. Methods DM1 was induced by intraperitoneal injection of streptozotocin 60 mg/kg body weight. Irisin in low dosage (5 µg twice a week for 6 weeks I/P) was injected into half of the control and 4-week diabetic male Wistar rats. Animals were sacrificed six months after induction of diabetes. The trabecular bone in the femoral head and neck was analyzed using a micro-CT technique. Bone turnover markers were measured using ELISA, Western blot, and RT-PCR techniques. Results It was found that DM1 deteriorates the trabecular bone microstructure by increasing trabecular separation (Tb-Sp) and decreasing trabecular thickness (Tb-Th), bone volume fraction (BV/TV), and bone mineral density (BMD). Irisin treatment positively affects bone quality by increasing trabecular number p < 0.05 and improves the BMD, Tb-Sp, and BV/TV by 21–28%. The deterioration in bone microarchitecture is mainly attributed to decreased bone formation observed as low osteocalcin and high sclerostin levels in diabetic bone samples p < 0.001. The irisin treatment significantly suppressed the serum and bone sclerostin levels p < 0.001, increased the serum CTX1 levels p < 0.05, and also showed non-significant improvement in osteocalcin levels. Conclusions This is the first pilot study to our knowledge that shows that a low dose of irisin marginally improves the trabecular bone in DM1 and is an effective peptide in reducing sclerostin levels.https://peerj.com/articles/16278.pdfDiabetesIrisinStreptozotocinTrabecular boneMicro-CTOsteoporosis
spellingShingle Sahar Mohsin
Fiona Brock
Suneesh Kaimala
Charlene Greenwood
Mohsin Sulaiman
Keith Rogers
Ernest Adeghate
A pilot study: effect of irisin on trabecular bone in a streptozotocin-induced animal model of type 1 diabetic osteopathy utilizing a micro-CT
PeerJ
Diabetes
Irisin
Streptozotocin
Trabecular bone
Micro-CT
Osteoporosis
title A pilot study: effect of irisin on trabecular bone in a streptozotocin-induced animal model of type 1 diabetic osteopathy utilizing a micro-CT
title_full A pilot study: effect of irisin on trabecular bone in a streptozotocin-induced animal model of type 1 diabetic osteopathy utilizing a micro-CT
title_fullStr A pilot study: effect of irisin on trabecular bone in a streptozotocin-induced animal model of type 1 diabetic osteopathy utilizing a micro-CT
title_full_unstemmed A pilot study: effect of irisin on trabecular bone in a streptozotocin-induced animal model of type 1 diabetic osteopathy utilizing a micro-CT
title_short A pilot study: effect of irisin on trabecular bone in a streptozotocin-induced animal model of type 1 diabetic osteopathy utilizing a micro-CT
title_sort pilot study effect of irisin on trabecular bone in a streptozotocin induced animal model of type 1 diabetic osteopathy utilizing a micro ct
topic Diabetes
Irisin
Streptozotocin
Trabecular bone
Micro-CT
Osteoporosis
url https://peerj.com/articles/16278.pdf
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