Proteomic and Transcriptomic Approaches for Studying Bone Regeneration in Health and Systemically Compromised Conditions

Abstract

Bone regeneration is a complex biological process, where the molecular mechanisms are only partially understood. In an ageing population, where the prevalence of chronic diseases with an impact on bone metabolism is increasing, it becomes crucial to identify new strategies that would improve regenerative outcomes also in medically compromised patients. In this context, omics are demonstrating a great potential, as they offer new insights on the molecular mechanisms regulating physiologic/pathologic bone healing and, at the same time, allow the identification of new diagnostic and therapeutic targets. This review provides an overview on the current evidence on the use of transcriptomic and proteomic approaches in bone regeneration research, particularly in relation to type 1 diabetes and osteoporosis, and discusses future scenarios and potential benefits and limitations on the integration of multi-omics. It is suggested that future research will leverage the synergy of omics with statistical modeling and bioinformatics to prompt the understanding of the biology underpinning bone formation in health and medically compromised conditions. With an eye toward personalized medicine, new strategies combining the mining of large datasets and bioinformatic data with a detailed characterization of relevant phenotypes will need to be pursued to further the understanding of disease mechanisms.

A Review of Recent Developments in the Molecular Mechanisms of Bone Healing

“…Transcriptomic and proteomic approaches have shown great potential in terms of bone regeneration because they offer new knowledge on the molecular physiological/pathological mechanisms that regulate bone consolidation [ 75 , 76 ]. Transcriptomic and proteomic approaches in bone regeneration research, particularly in relation to type 1 diabetes and osteoporosis, appear to be important in current practice [ 77 ].…”

Bone Phenotyping Approaches in Human, Mice and Zebrafish – Expert Overview of the EU Cost Action GEMSTONE (“GEnomics of MusculoSkeletal traits TranslatiOnal NEtwork”)

“…For instance, proteomic approaches can help detect changes in the signal transduction of bone cells, in the regulatory mechanisms that govern bone cell differentiation, among other cellular and tissue processes enrolled in bone metabolism in both physiologic and pathological contexts (297). Accordingly up to now, several studies have made important contributions to our knowledge of the bone proteome, as well as, of the proteomes of individual bone cells (reviewed in (297)(298)(299). A special emphasis has been given to identify proteomic changes in osteoporosis (300).…”

Towards in silico Models of the Inflammatory Response in Bone Fracture Healing

“…To explore cellular processes in bone biology, omics technologies characterize, among others, DNA modifications (epigenomics), RNA transcriptions (transcriptomics), protein synthesis (proteomics) and metabolic activity (metabolomics) ( Reppe et al, 2017 ). Transcriptomics, proteomics and metabolomics provide a direct measure of cell survival, proliferation, differentiation and phenotype ( Calciolari and Donos, 2020 ). Therefore, omics technologies can validate in silico models of bone healing by coupling cellular function to tissue adaptation ( Figure 3B ).…”

“…Regarding transcriptomics, RNA sequencing (RNA-seq) technologies measure whole transcriptomes, thus they simultaneously analyze the gene expression profile of thousands of genes ( Stark et al, 2019 ; Calciolari and Donos, 2020 ). When applied to fracture healing, RNA-seq revealed differences in gene expression associated to skeletal and vascular formation between two mice strains, which was correlated to differences in endochondral bone formation ( Grimes et al, 2011 ).…”