In Vitro Weight-Loaded Cell Models for Understanding Mechanodependent Molecular Pathways Involved in Orthodontic Tooth Movement: A Systematic Review

Abstract

Cells from the mesenchymal lineage in the dental area, including but not limited to PDL fibroblasts, osteoblasts, and dental stem cells, are exposed to mechanical stress in physiological (e.g., chewing) and nonphysiological/therapeutic (e.g., orthodontic tooth movement) situations. Close and complex interaction of these different cell types results in the physiological and nonphysiological adaptation of these tissues to mechanical stress. Currently, different in vitro loading models are used to investigate the effect of different types of mechanical loading on the stress adaptation of these cell types. We performed a systematic review according to the PRISMA guidelines to identify all studies in the field of dentistry with focus on mechanobiology using in vitro loading models applying uniaxial static compressive force. Only studies reporting on cells from the mesenchymal lineage were considered for inclusion. The results are summarized regarding gene expression in relation to force duration and magnitude, and the most significant signaling pathways they take part in are identified using protein-protein interaction networks.

Current Trends in In Vitro Modeling to Mimic Cellular Crosstalk in Periodontal Tissue

“…[37,38] During mechanical loading and OTM, alteration of the ECM features occurs due to a release of soluble factors, that may exhibit either positive or negative effects on PDL remodeling and eventually trigger a local inflammatory response. [39][40][41][42] Periodontal ligament fibroblasts (PDLFs), PDLSCs, and cementoblasts have been investigated in in vitro and in vivo models focusing on the secretion of cytokines and growth factors turnover during remodeling and regeneration. [10,43] All of these modifications inevitably activate mechanotransduction signals that advance the internal signal propagation cascades and gene transcription.…”

“…[44,45] In addition to activation of the Wnt pathway, mechanical loading results in cytoskeletal rearrangements when the mechanosensory protein complex is linked to a kinase cascade system. [39] The mechanosensory protein complex contains Talin, Vinculin, Tensin, Paxillin, Src, and focal adhesion kinase (FAK). Activated extracellular signal-regulated protein kinase (ERK) then enters the nucleus triggering the transcription of several additional regulatory genes.…”

Development of a 3D human osteoblast cell culture model for studying mechanobiology in orthodontics

“…Mechanical stress applied here were from 1g/cm 2 to 4g/cm 2 . This is in the range of the most commonly applied forces in orthodontic weight-loaded approach models (16).…”

“…As several studies demonstrate their variation according to the mechanical stress imposed on cells, markers of osteoblastic activity were analysed by qRT-PCR (16). We used two reference genes according to the work of Vazquez and Rauh: 18S and HPRT (24,25).…”

“…The complexity of in A c c e p t e d M a n u s c r i p t vivo studies makes analysing these communication channels difficult. As a result, models using cells isolated from alveolar bone have been established to simulate the application of orthodontic forces (16). Currently, cell culture is widely used in biomedical research to better elucidate the physiology, pathology and therapy of many processes and diseases.…”