Integrin α10 regulates adhesion, migration, and osteogenic differentiation of alveolar bone marrow mesenchymal stem cells in type 2 diabetic patients who underwent dental implant surgery

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ABSTRACT

Type 2 diabetes mellitus (T2DM) is a clinically important risk factor for dental implant treatment failure. An imbalance in the microenvironment of the jawbone of diabetic patients can impair the functions of bone marrow mesenchymal stem cells (BMSCs), thereby interfering with implant osseointegration during the healing phase. This study aims to investigate potential molecular factors associated with abnormal BMSC biological functions in diabetic patients with dental implant failure and identify intervention targets to improve implant osseointegration. The results of cell adhesion, cell scratch migration, alkaline phosphatase (ALP) activity, alizarin red staining, and real-time PCR assays showed that the adhesion, migration, and osteogenic differentiation abilities were significantly lower in alveolar BMSCs isolated from diabetic patients with implant failure (DM-F group) than in those isolated from diabetic patients with implant success (DM-S group) and normal patients (Nor group). Also, bioinformatics analysis and verification of whole-cell proteomics results revealed that integrin subunit alpha10 (ITGA10) expression in BMSCs was significantly lower in the DM-F group than in the DM-S group and much lower than that in the Nor group. In addition, lentiviral mediated short hairpin RNA (shRNA) or complementary DNA (cDNA) was used to knockdown or overexpress ITGA10 in BMSCs from diabetic patients, and the results revealed that ITGA10 knockdown significantly reduced the adhesion and migration abilities of BMSCs and inhibited their osteogenic differentiation potential by disturbing the FAK/PI3K/AKT/GSK3β/β-catenin pathway. ITGA10 overexpression produced the opposite results. In summary, this study revealed that low ITGA10 expression in BMSCs from the DM-F group is a major cause of cell dysfunction, including reduction in the adhesion, migration, and osteogenic differentiation abilities of BMSCs, and provided insight into the underlying mechanism. Additionally, ITGA10 was identified as a potential target protein for improving the biological functions of BMSCs and dental implant osseointegration in T2DM patients.

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Pathophysiology of Type 2 Diabetes Mellitus

Unai Galicia-Garcia, Asier Benito-Vicente, Shifa Jebari … (2020)

Type 2 Diabetes Mellitus (T2DM), one of the most common metabolic disorders, is caused by a combination of two primary factors: defective insulin secretion by pancreatic β-cells and the inability of insulin-sensitive tissues to respond appropriately to insulin. Because insulin release and activity are essential processes for glucose homeostasis, the molecular mechanisms involved in the synthesis and release of insulin, as well as in its detection are tightly regulated. Defects in any of the mechanisms involved in these processes can lead to a metabolic imbalance responsible for the development of the disease. This review analyzes the key aspects of T2DM, as well as the molecular mechanisms and pathways implicated in insulin metabolism leading to T2DM and insulin resistance. For that purpose, we summarize the data gathered up until now, focusing especially on insulin synthesis, insulin release, insulin sensing and on the downstream effects on individual insulin-sensitive organs. The review also covers the pathological conditions perpetuating T2DM such as nutritional factors, physical activity, gut dysbiosis and metabolic memory. Additionally, because T2DM is associated with accelerated atherosclerosis development, we review here some of the molecular mechanisms that link T2DM and insulin resistance (IR) as well as cardiovascular risk as one of the most important complications in T2DM.

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Effects of titanium surface topography on bone integration: a systematic review.

Ann Wennerberg, Tomas Albrektsson (2009)

To analyse possible effects of titanium surface topography on bone integration. Our analyses were centred on a PubMed search that identified 1184 publications of assumed relevance; of those, 1064 had to be disregarded because they did not accurately present in vivo data on bone response to surface topography. The remaining 120 papers were read and analysed, after removal of an additional 20 papers that mainly dealt with CaP-coated and Zr implants; 100 papers remained and formed the basis for this paper. The bone response to differently configurated surfaces was mainly evaluated by histomorphometry (bone-to-implant contact), removal torque and pushout/pullout tests. A huge number of the experimental investigations have demonstrated that the bone response was influenced by the implant surface topography; smooth (S(a) 1-2 microm) surfaces showed stronger bone responses than rough (S(a)>2 microm) in some studies. One limitation was that it was difficult to compare many studies because of the varying quality of surface evaluations; a surface termed 'rough' in one study was not uncommonly referred to as 'smooth' in another; many investigators falsely assumed that surface preparation per se identified the roughness of the implant; and many other studies used only qualitative techniques such as SEM. Furthermore, filtering techniques differed or only height parameters (S(a), R(a)) were reported. * Surface topography influences bone response at the micrometre level. * Some indications exist that surface topography influences bone response at the nanometre level. * The majority of published papers present an inadequate surface characterization. * Measurement and evaluation techniques need to be standardized. * Not only height descriptive parameters but also spatial and hybrid ones should be used.

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Mediation of biomaterial-cell interactions by adsorbed proteins: a review.

Cameron J Wilson, Richard E Clegg, David I Leavesley … (2005)

An appropriate cellular response to implanted surfaces is essential for tissue regeneration and integration. It is well described that implanted materials are immediately coated with proteins from blood and interstitial fluids, and it is through this adsorbed layer that cells sense foreign surfaces. Hence, it is the adsorbed proteins, rather than the surface itself, to which cells initially respond. Diverse studies using a range of materials have demonstrated the pivotal role of extracellular adhesion proteins--fibronectin and vitronectin in particular--in cell adhesion, morphology, and migration. These events underlie the subsequent responses required for tissue repair, with the nature of cell surface interactions contributing to survival, growth, and differentiation. The pattern in which adhesion proteins and other bioactive molecules adsorb thus elicits cellular reactions specific to the underlying physicochemical properties of the material. Accordingly, in vitro studies generally demonstrate favorable cell responses to charged, hydrophilic surfaces, corresponding to superior adsorption and bioactivity of adhesion proteins. This review illustrates the mediation of cell responses to biomaterials by adsorbed proteins, in the context of osteoblasts and selected materials used in orthopedic implants and bone tissue engineering. It is recognized, however, that the periimplant environment in vivo will differ substantially from the cell-biomaterial interface in vitro. Hence, one of the key issues yet to be resolved is that of the interface composition actually encountered by osteoblasts within the sequence of inflammation and bone regeneration.

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Journal

Journal ID (nlm-ta): Bioengineered

Journal ID (iso-abbrev): Bioengineered

Title: Bioengineered

Publisher: Taylor & Francis

ISSN (Print): 2165-5979

ISSN (Electronic): 2165-5987

Publication date (Electronic, pub): 29 May 2022

Publication date (Electronic, collection): 2022

Publication date PMC-release: 29 May 2022

Volume: 13

Issue: 5

Pages: 13252-13268

Affiliations

[a ]Department of Dental Implant Center, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University; , Beijing, China

[b ]Beijing Institute of Dental Research, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University; , Beijing, China

Author notes

CONTACT Jun Li lijun3021@ 123456aliyun.com Department of Dental Implant Center, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University; , Beijing 100050, China

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Jun Li https://orcid.org/0000-0002-9301-6073

Article

Publisher ID: 2079254

DOI: 10.1080/21655979.2022.2079254

PMC ID: 9275886

PubMed ID: 35635091

SO-VID: bc7f60f8-29e3-439b-86a6-c3c4ba8955d7

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This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Integrin α10 regulates adhesion, migration, and osteogenic differentiation of alveolar bone marrow mesenchymal stem cells in type 2 diabetic patients who underwent dental implant surgery

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Most cited references 53

Pathophysiology of Type 2 Diabetes Mellitus

Effects of titanium surface topography on bone integration: a systematic review.

Mediation of biomaterial-cell interactions by adsorbed proteins: a review.

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