Role of Fibroblast Populations in Periodontal Wound Healing and Tissue Remodeling.

Published on Apr 24, 2019in Frontiers in Physiology3.367
· DOI :10.3389/FPHYS.2019.00270
Patricio C. Smith22
Estimated H-index: 22
(UC: Pontifical Catholic University of Chile),
Constanza Martínez12
Estimated H-index: 12
(UC: Pontifical Catholic University of Chile)
+ 1 AuthorsChristopher A. McCulloch86
Estimated H-index: 86
(U of T: University of Toronto)
Sources
Abstract
After injury to periodontal tissues a healing response is initiated that includes a series of sequential phases, which enable wound closure and partial restoration of tissue structure and function. Wound closure in periodontal tissues involves the tightly regulated coordination of resident cells in epithelial and connective tissue compartments. Multiple cell populations in these compartments synergize their metabolic activities to re-establish a mucosal seal that involves the underlying periodontal connective tissues and the tooth surface. The formation of an impermeable seal around the circumference of the tooth is of particular significance in oral health since inappropriate colonization of tooth surfaces by pathogenic biofilms promotes inflammation, which can contribute to periodontal tissue degradation and tooth loss. The reformation of periodontal tissue structures centrally involves fibroblasts, which synthesize and organize the collagen fibers that link alveolar bone and gingiva to the cementum covering the tooth root. The synthesis and remodeling of nascent collagen matrices are of fundamental importance for the re-establishment of a functional periodontium after tissue destruction and are mediated by diverse, multi-functional fibroblast populations that reside within the connective tissues of gingiva and periodontal ligament. Notably, after gingival wounding, a fibroblast sub-type (myofibroblast) arises, which is centrally involved in collagen synthesis and fibrillar remodeling. While myofibroblasts are not usually seen in healthy, mature connective tissues, their formation is increased by wound-healing cytokines and is modulated by the stiffness of the extracellular matrix, which is mechanosensed by resident precursor cells in the gingival connective tissue microenvironment. Here we consider the cellular origins and the factors that control the differentiation and matrix remodeling functions of periodontal fibroblasts. An improved understanding of the regulation and function of periodontal fibroblasts will be critical for the development of new therapies to optimize the restoration of periodontal structure and function after wounding.
Download
📖 Papers frequently viewed together
128 Citations
20 Citations
1989
References50
Newest
#1Ruth Ellen Jones (Stanford University)H-Index: 8
#2Deshka S. Foster (Stanford University)H-Index: 10
Last. Michael T. Longaker (Stanford University)H-Index: 137
view all 3 authors...
55 CitationsSource
#1Emanuel Rognoni ('KCL': King's College London)H-Index: 17
#2Angela Oliveira Pisco ('KCL': King's College London)H-Index: 22
Last. Fiona M. Watt ('KCL': King's College London)H-Index: 124
view all 9 authors...
Abstract Murine dermis contains functionally and spatially distinct fibroblast lineages that cease to proliferate in early postnatal life. Here, we propose a model in which a negative feedback loop between extracellular matrix (ECM) deposition and fibroblast proliferation determines dermal architecture. Virtual‐tissue simulations of our model faithfully recapitulate dermal maturation, predicting a loss of spatial segregation of fibroblast lineages and dictating that fibroblast migration is only ...
52 CitationsSource
#1Ignacio N. Retamal (UC: Pontifical Catholic University of Chile)H-Index: 6
#2Romina Hernández (UC: Pontifical Catholic University of Chile)H-Index: 3
Last. Patricio C. Smith (UC: Pontifical Catholic University of Chile)H-Index: 22
view all 7 authors...
Background: Glucose-derived metabolites may alter the structure and biologic properties of important proteins in periodontium, such as collagens. As a consequence, it is possible that collagen-binding cells may change their phenotypic traits. Although the glucose-derived product methylglyoxal (MGO) has been detected in periodontal lesions, the precise effect of collagen glycation on gingival connective tissue biology is not fully understood. The present study evaluates whether collagen glycation...
5 CitationsSource
#1Nuno M. Coelho (U of T: University of Toronto)H-Index: 10
#2Pamma D. Arora (U of T: University of Toronto)H-Index: 15
Last. Christopher A. McCulloch (U of T: University of Toronto)H-Index: 86
view all 8 authors...
Summary Discoidin domain receptor 1 (DDR1) is a tyrosine kinase collagen adhesion receptor that mediates cell migration through association with non-muscle myosin IIA (NMIIA). Because DDR1 is implicated in cancer fibrosis, we hypothesized that DDR1 interacts with NMIIA to enable collagen compaction by traction forces. Mechanical splinting of rat dermal wounds increased DDR1 expression and collagen alignment. In periodontal ligament of DDR1 knockout mice, collagen mechanical reorganization was re...
46 CitationsSource
#1Kerstin Klinkert (UCC: University College Cork)H-Index: 2
#2Derek WhelanH-Index: 7
Last. Noel M. CapliceH-Index: 53
view all 6 authors...
Background: A prolonged inflammatory phase is seen in aberrant wound healing and in chronic wounds. Macrophages are central to wound healing. Distinct macrophage
38 CitationsSource
#1B. Hinz (U of T: University of Toronto)H-Index: 1
Abstract The importance of proper skin wound healing becomes evident when our body's repair mechanisms fail, leading to either non-healing (chronic) wounds or excessive repair (fibrosis). Chronic wounds are a tremendous burden for patients and global healthcare systems and are on the rise due to their increasing incidence with age and diabetes. Curiously, these same risk factors also sign responsible for the development of hypertrophic scarring and organ fibrosis. Activated repair cells – myofib...
118 CitationsSource
#1Nuno M. Coelho (U of T: University of Toronto)H-Index: 10
#2Christopher A. McCulloch (U of T: University of Toronto)H-Index: 86
Fibrosis is the result of a wound-healing response that fails to restore normal tissue structure function. One of the critical hallmarks of fibrosis is disrupted collagen remodeling. In tissue homeostasis, the production, deposition and organization of collagen is balanced by the degradation and remodeling of collagen within the existing matrix. After injury or chronic infection, tissues initiate a wound-healing response that is intended to create a new ECM for restoring tissue structure and fun...
40 CitationsSource
#1Constanza Martínez (UC: Pontifical Catholic University of Chile)H-Index: 12
#2Sergio González (University of Chile)H-Index: 29
Last. Patricio C. Smith (UC: Pontifical Catholic University of Chile)H-Index: 22
view all 4 authors...
Background: Plasma-derived fractions have been used as an autologous source of growth factors; however, limited knowledge concerning their biologic effects has hampered their clinical application. In this study, the authors analyze the content and specific effect of both platelet-rich plasma (PRP) and platelet-poor plasma (PPP) on osteoblastic differentiation using primary cultures of human periodontal ligament stem cells (HPLSCs).Methods: The authors evaluated the growth factor content of PRP a...
19 CitationsSource
#1Benjamin Fournier (UBC: University of British Columbia)H-Index: 14
Last. Lari HäkkinenH-Index: 41
view all 6 authors...
Abstract Neural crest (NC)-derived stem cells (NCSC) have an exceptionally wide differentiation potential, but their use in regenerative therapy has been hampered by their scarcity in adult tissues and complex isolation protocols. Human oral mucosal gingiva may provide an attractive source of these cells as it contains NC-derived cells, the tissue is easily accessible and wound healing is fast and scarless with very little morbidity. To this end, we first investigated whether NC-derived cells ar...
33 CitationsSource
#1Seok-Joon Jin (Catholic University of Korea)H-Index: 7
#2Jeongjin Lee (Catholic University of Korea)H-Index: 14
Last. Jun-Beom Park (Catholic University of Korea)H-Index: 27
view all 6 authors...
Background and Objective The main purpose of this study was to isolate and characterize gingival connective tissue-derived mesenchymal stem cells (GMSCs). The secondary purpose was to present a modified isolation method for the GMSCs. Material and Methods Collected healthy gingival tissue samples were de-epithelialized and minced into small fragments. The tissues were digested by dispase and collagenase IV for 30 min. The first digested cell suspension was discarded, and then additional digestio...
79 CitationsSource
Cited By39
Newest
#1Julia Guerrero-Gironés (University of Murcia)H-Index: 7
Last. David García-BernalH-Index: 21
view all 5 authors...
Abstract null null Aims null To analyze the biological effects of the cements Relyx Unicem 2, Panavia V5, Multilink Hybrid Abutment and SoloCem on human gingival fibroblast cells (HGFs). null null null Materials and Methods null HGFs were exposed to different eluates (n=40) of the studied resin-based cements. Their cytotoxic effects and influence on cell migration were assessed using MTT and wound-healing assays, respectively. Level of HGF attachment, cell morphology and F-actin cytoskeleton con...
Source
#1Takeyoshi Asakawa (Showa University)H-Index: 5
#2Atsushi Yamada (Showa University)H-Index: 19
Last. Tomomi Sugiyama (Showa University)
view all 12 authors...
Down’s syndrome is one of the most common human congenital genetic diseases and affected patients have increased risk of periodontal disease. To examine involvement of the disease with periodontal disease development, we established immortalized periodontal ligament cells obtained from a Down’s syndrome patient by use of SV40T-Ag and hTERT gene transfection. Expressions of SV40T-Ag and hTERT were observed in periodontal ligament cell-derived immortalized cells established from healthy (STPDL) an...
Source
#2Evgenia Kogan (MSMU: I.M. Sechenov First Moscow State Medical University)H-Index: 1
view all 10 authors...
Soft gingival tissue deficiency remains a severe problem leading to postoperative recession, peri-implantitis, and bone resorption. The use of collagen matrices does not always lead to complete rebuilding of the gingiva volume. The application of mesenchymal stromal cells (MSCs) simultaneously with collagen materials represents a promising approach for the restoration of soft gingival tissues. However, short-term effects of MSCs-enriched collagen grafts after gingival augmentation have not yet b...
Source
#1Chao-Yen Huang (CSMU: Chung Shan Medical University)
#2Pei-Ling Hsieh (China Medical University (Taiwan))H-Index: 12
Last. Taichen Lin (CSMU: Chung Shan Medical University)H-Index: 5
view all 6 authors...
Periodontitis is a progressive inflammation condition and a primary cause of tooth loss in adults. As one of the abundant cell types in the periodontium, periodontal ligament fibroblasts (PDLFs) play an integral role in the maintenance and regeneration of periodontal tissue. Our previous work has shown that the application of Er:YAG laser increased the cell proliferation and migratory capacity of PDLFs via induction of galectin-7. In the present study, we aimed to evaluate if the forced expressi...
Source
#1Atieh Abedin-DoH-Index: 6
#2Ze ZhangH-Index: 30
Last. Mahmoud RouabhiaH-Index: 46
view all 5 authors...
Diabetic foot ulcers are indicative of an impaired wound healing process. This delay may be resolved through electrical stimulation (ES). The goal of the present study was to evaluate the effect of ES on diabetic fibroblast adhesion and growth, and the secretion of cytokines and growth factors. Diabetic human skin fibroblasts (DHSF) were exposed to various intensities of direct current ES (100, 80, 40 and 20 mV/mm). The effect of ES on fibroblast adhesion and growth was evaluated using Hoechst s...
Source
#1Chunxia Qin (HUST: Huazhong University of Science and Technology)H-Index: 12
#2Yangmeihui Song (HUST: Huazhong University of Science and Technology)H-Index: 1
Last. Xiaoli LanH-Index: 17
view all 9 authors...
Source
#1Pierfrancesco Pagella (UZH: University of Zurich)H-Index: 13
#2Laura De Vargas Roditi (UZH: University of Zurich)H-Index: 5
Last. Thimios A. Mitsiadis (UZH: University of Zurich)H-Index: 53
view all 5 authors...
The Notch signaling pathway is a fundamental regulator of cell fate determination in homeostasis and regeneration. In this work, we aimed to determine how Notch signaling mediates the interactions between perivascular stem cells and their niches in human dental mesenchymal tissues, both in homeostatic and regenerative conditions. By single cell RNA sequencing analysis, we showed that perivascular cells across the dental pulp and periodontal human tissues all express NOTCH3, and that these cells ...
Source
#1Feng Wang (Tongji University)H-Index: 1
#2Shu-guang Wang (Tongji University)
Last. Liang Zhang (YZU: Yangzhou University)H-Index: 9
view all 7 authors...
Abstract null null Objective null In spinal surgery, considerable blood loss is increasingly treated with local application of TXA. However, little is known about the cytotoxicity and effect on human fibroblasts. This study was to identify the effect of TXA solutions on human fibroblast at different concentrations and exposure times in vitro. null null null Methods null To mimic the actual clinical situation, human fibroblast was subjected to both limited and chronic exposure to various clinical...
Source
#1Jazli Aziz (UM: University of Malaya)H-Index: 3
#2Mohammad Tariqur Rahman (UM: University of Malaya)H-Index: 14
Last. Rathna Devi Vaithilingam (UM: University of Malaya)H-Index: 9
view all 3 authors...
BACKGROUND Periodontitis (PD) is a multifaceted inflammatory disease connected to bacterial infection that results in the destruction of tooth supporting structures and eventually tooth loss. Given their involvement in infection and inflammation, both metallothionein (MT) and zinc (Zn) might play vital roles in the development and progression of PD. More specifically, both MT and Zn are heavily involved in regulating immune functions, controlling bacterial infection, balancing inflammatory respo...
1 CitationsSource
#1David Fraser (UR: University of Rochester)H-Index: 4
#2Tram Nguyen (UR: University of Rochester)
Last. Danielle S. W. Benoit (UR: University of Rochester)H-Index: 34
view all 3 authors...
Rebuilding the tooth-supporting tissues (periodontium) destroyed by periodontitis remains a clinical challenge. Periodontal ligament cells (PDLCs), multipotent cells within the periodontal ligament (PDL), differentiate and form new PDL and mineralized tissues (cementum and bone) during native tissue repair in response to specific extracellular matrix (ECM) cues. Thus, harnessing ECM cues to control PDLC activity ex vivo, and ultimately, to design a PDLC delivery vehicle for tissue regeneration i...
Source