Hyperglycemia exerts disruptive effects on the secretion of TGF‐β1 and its matrix ligands, decorin and biglycan by mesenchymal sub-populations and macrophages during bone repair

Yusop, Norhayati, Moseley, Ryan ORCID: https://orcid.org/0000-0002-2812-6735 and Waddington, Rachel J. ORCID: https://orcid.org/0000-0001-5878-1434 2023. Hyperglycemia exerts disruptive effects on the secretion of TGF‐β1 and its matrix ligands, decorin and biglycan by mesenchymal sub-populations and macrophages during bone repair. Frontiers in Dental Medicine 4 10.3389/fdmed.2023.1200122

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Abstract

Bone has a high capacity for repair, but for patients with uncontrolled type 2 diabetes mellitus (T2DM), the associated hyperglycemia can significantly delay osteogenic processes. These patients respond poorly to fracture repair and bone grafts, leading to lengthy care-plans due to arising complications. Mesenchymal stromal cells (MSCs) and M2 macrophages are both major sources of transforming growth factor-β1 (TGF-β1), a recognized mediator for osteogenesis and whose bioavailability and activities are further regulated by matrix small leucine-rich proteoglycans (SLRPs), decorin and biglycan. The aim of this study was to investigate how in vivo and in vitro hyperglycemic environments can influence levels of TGF-β1, decorin and biglycan during bone repair; with additional consideration for how long-term glucose exposure and cell ageing can also influence this process. Following bone healing in a T2DM in vivo model, histological and immuno-labeling analyses of bone tissue sections confirmed delayed healing, which was associated with significantly elevated TGF-β1 levels within the bone matrices of young diabetic rats, compared with normoglycemic and aged counterparts. Studies continued to assess in vitro effects of normal (5.5 mM) and high (25 mM) glucose exposure on osteogenic differentiation of compact bone derived mesenchymal stromal cells (CB-MSCs) at population doubling (PD)15, characterized to contain populations of lineage committed osteoblasts and at PD150, where transit amplifying cells predominate. Short-term glucose exposure increased TGF-β1 and decorin secretion by committed osteoblasts, but had lesser effect on transit amplifying cells. In contrast, long-term exposure of CB-MSCs to high glucose was associated with decreased TGF-β1 and increased decorin secretion. Similar assessments on macrophage populations indicated high glucose inhibited TGF-β1 secretion, preventing M2 formation. Collectively, these findings highlight how hyperglycemia associated with T2DM can perturb TGF-β1 and decorin secretion by MSCs and macrophages, thereby potentially influencing TGF-β1 bioavailability and signaling during bone repair.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Dentistry
Publisher:	Frontiers Media
ISSN:	2673-4915
Date of First Compliant Deposit:	12 June 2023
Date of Acceptance:	5 June 2023
Last Modified:	29 Jun 2023 12:52
URI:	https://orca.cardiff.ac.uk/id/eprint/160318

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