Therapeutic Potential of BMP7 in the Treatment of Osteoporosis Caused by the Interaction between Inflammation and Corticosteroids in Inflammatory Bowel Disease

Individuals with inflammatory bowel disease (IBD) have an increased risk of bone impairment, which is a process controlled by the RANKL/RANK/OPG system, mostly due to chronic inflammation and corticosteroid treatment. Bone morphogenic protein 7 (BMP7) has a complex role in maintaining inflammation a...

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Main Authors: Ivana Smoljan, Dijana Detel, Suncica Buljevic, Igor Erjavec, Ivana Marić
Format: Article
Language:English
Published: MDPI AG 2023-08-01
Series:Biomedicines
Subjects:
Online Access:https://www.mdpi.com/2227-9059/11/8/2161
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author Ivana Smoljan
Dijana Detel
Suncica Buljevic
Igor Erjavec
Ivana Marić
author_facet Ivana Smoljan
Dijana Detel
Suncica Buljevic
Igor Erjavec
Ivana Marić
author_sort Ivana Smoljan
collection DOAJ
description Individuals with inflammatory bowel disease (IBD) have an increased risk of bone impairment, which is a process controlled by the RANKL/RANK/OPG system, mostly due to chronic inflammation and corticosteroid treatment. Bone morphogenic protein 7 (BMP7) has a complex role in maintaining inflammation and bone remodeling but little is known about its anti-inflammatory potential in chronic colitis. We investigated the effect of systemically administered BMP7 and corticosteroids on the severity of inflammation, macrophage differentiation, and bone regeneration in a chronic IBD model. Methods: Chronic colitis was induced in male Sprague Dawley rats via weekly administration of 2,4,6-trinitrobenzenesulfonic acid over 21 days following BMP7 or corticosteroid treatment for five days. The levels of serum and colon tissue inflammatory cytokines, RANKL/OPG system, as well as markers of macrophage polarization, were detected using RT-PCR, ELISA, or immunohistochemistry. Long bone and spine analyses were performed using microcomputed tomography (micro-CT). Results: The administration of BMP7 reduced the adverse effects of colitis and led to elevated OPG and RANK in the colon with a simultaneous decrease in TNF-α and an increase in IL-10 and TGF-β. Decreased expression of the M2 macrophage marker CD163 was found in the BMP7-treated rats compared with the colitis group, whereas the number of M1 marker iNOS-positive cells did not differ between the groups. As a result of the BMP7 treatment, morphometric parameters of trabecular bone increased, and increased trabecular separation noted in the colitis group did not appear. Conclusions: We showed that BMP7 suppressed the inflammatory response in chronic colitis, mainly by shifting the cytokine balance and by triggering alterations in the RANKL/OPG system rather than through a macrophage polarization imbalance. In addition, considering the demonstrated effect of BMP7 on bone morphology and structure, it can be suggested that BMP7 plays a role in the managing of osteoporosis in chronic colitis, and thus, its therapeutic potential in the treatment of IBD should be further evaluated.
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spelling doaj.art-d8635526cba5497395e8bfb49db32cb92023-11-19T00:20:15ZengMDPI AGBiomedicines2227-90592023-08-01118216110.3390/biomedicines11082161Therapeutic Potential of BMP7 in the Treatment of Osteoporosis Caused by the Interaction between Inflammation and Corticosteroids in Inflammatory Bowel DiseaseIvana Smoljan0Dijana Detel1Suncica Buljevic2Igor Erjavec3Ivana Marić4Department of Internal Medicine, Faculty of Medicine, University of Rijeka, Brace Branchetta 20, 51000 Rijeka, CroatiaDepartment of Medical Chemistry, Biochemistry and Clinical Chemistry, Faculty of Medicine, University of Rijeka, Brace Branchetta 20, 51000 Rijeka, CroatiaDepartment of Medical Chemistry, Biochemistry and Clinical Chemistry, Faculty of Medicine, University of Rijeka, Brace Branchetta 20, 51000 Rijeka, CroatiaLaboratory of Mineralized Tissues, Center for Translational and Clinical Research, School of Medicine, University of Zagreb, 10000 Zagreb, CroatiaDepartment of Anatomy, Faculty of Medicine, University of Rijeka, Brace Branchetta 20, 51000 Rijeka, CroatiaIndividuals with inflammatory bowel disease (IBD) have an increased risk of bone impairment, which is a process controlled by the RANKL/RANK/OPG system, mostly due to chronic inflammation and corticosteroid treatment. Bone morphogenic protein 7 (BMP7) has a complex role in maintaining inflammation and bone remodeling but little is known about its anti-inflammatory potential in chronic colitis. We investigated the effect of systemically administered BMP7 and corticosteroids on the severity of inflammation, macrophage differentiation, and bone regeneration in a chronic IBD model. Methods: Chronic colitis was induced in male Sprague Dawley rats via weekly administration of 2,4,6-trinitrobenzenesulfonic acid over 21 days following BMP7 or corticosteroid treatment for five days. The levels of serum and colon tissue inflammatory cytokines, RANKL/OPG system, as well as markers of macrophage polarization, were detected using RT-PCR, ELISA, or immunohistochemistry. Long bone and spine analyses were performed using microcomputed tomography (micro-CT). Results: The administration of BMP7 reduced the adverse effects of colitis and led to elevated OPG and RANK in the colon with a simultaneous decrease in TNF-α and an increase in IL-10 and TGF-β. Decreased expression of the M2 macrophage marker CD163 was found in the BMP7-treated rats compared with the colitis group, whereas the number of M1 marker iNOS-positive cells did not differ between the groups. As a result of the BMP7 treatment, morphometric parameters of trabecular bone increased, and increased trabecular separation noted in the colitis group did not appear. Conclusions: We showed that BMP7 suppressed the inflammatory response in chronic colitis, mainly by shifting the cytokine balance and by triggering alterations in the RANKL/OPG system rather than through a macrophage polarization imbalance. In addition, considering the demonstrated effect of BMP7 on bone morphology and structure, it can be suggested that BMP7 plays a role in the managing of osteoporosis in chronic colitis, and thus, its therapeutic potential in the treatment of IBD should be further evaluated.https://www.mdpi.com/2227-9059/11/8/2161inflammatory bowel diseasebone morphogenetic proteinsnuclear factor-κB ligand activatorosteoprotegerincytokinesmacrophage activation
spellingShingle Ivana Smoljan
Dijana Detel
Suncica Buljevic
Igor Erjavec
Ivana Marić
Therapeutic Potential of BMP7 in the Treatment of Osteoporosis Caused by the Interaction between Inflammation and Corticosteroids in Inflammatory Bowel Disease
Biomedicines
inflammatory bowel disease
bone morphogenetic proteins
nuclear factor-κB ligand activator
osteoprotegerin
cytokines
macrophage activation
title Therapeutic Potential of BMP7 in the Treatment of Osteoporosis Caused by the Interaction between Inflammation and Corticosteroids in Inflammatory Bowel Disease
title_full Therapeutic Potential of BMP7 in the Treatment of Osteoporosis Caused by the Interaction between Inflammation and Corticosteroids in Inflammatory Bowel Disease
title_fullStr Therapeutic Potential of BMP7 in the Treatment of Osteoporosis Caused by the Interaction between Inflammation and Corticosteroids in Inflammatory Bowel Disease
title_full_unstemmed Therapeutic Potential of BMP7 in the Treatment of Osteoporosis Caused by the Interaction between Inflammation and Corticosteroids in Inflammatory Bowel Disease
title_short Therapeutic Potential of BMP7 in the Treatment of Osteoporosis Caused by the Interaction between Inflammation and Corticosteroids in Inflammatory Bowel Disease
title_sort therapeutic potential of bmp7 in the treatment of osteoporosis caused by the interaction between inflammation and corticosteroids in inflammatory bowel disease
topic inflammatory bowel disease
bone morphogenetic proteins
nuclear factor-κB ligand activator
osteoprotegerin
cytokines
macrophage activation
url https://www.mdpi.com/2227-9059/11/8/2161
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