Leveraging Proteomics and Proteogenomics for Understanding Osteoporosis and Other Musculoskeletal Diseases.

Masashi Hasebe, Chen-Yang Su, Douglas P Kiel, Satoshi Yoshiji

Journal: Current osteoporosis reports 2025;23(1):43

PMID: 41073837

Abstract

PURPOSE OF REVIEW

Osteoporosis and musculoskeletal diseases, including osteoarthritis and sarcopenia, contribute substantially to global morbidity and healthcare costs. This review explores how proteogenomics integrates genomic and proteomic data to refine disease classification, identify causal pathways, and accelerate biomarker and drug target discovery.

RECENT FINDINGS

Large-scale proteomic studies, including UK Biobank-based research, have identified circulating proteins associated with musculoskeletal disease risk and progression. Proteomic risk models outperform conventional clinical metrics in predicting outcomes. Genomics, proteomics, and proteogenomics have facilitated the identification of causal markers through methods such as genome-wide association studies, effector gene mapping, and proteome-wide Mendelian randomization. Pathways implicated in disease mechanisms include extracellular matrix remodeling (e.g., COL6A3, COL9A1), metabolic regulation (e.g., IGFBP2, GDF15), inflammatory processes (e.g., TNF family ligands, CXCL17), and sex-hormone-related signaling (e.g., FSHB, SHBG). While these biological processes contribute across osteoporosis, osteoarthritis, and sarcopenia, distinct proteins have also been linked to disease-specific pathophysiology, offering potential therapeutic targets. Genomics, proteomics, and proteogenomics refine our understanding of musculoskeletal conditions and hold strong potential for improving early diagnosis, enhancing risk stratification, and advancing precision treatments.

Address: Department of Human Genetics, McGill University, 740 Avenue Dr. Penfield, Montréal, Québec, H3A 0G1, Canada.; Canada Excellence Research Chair in Genomic Medicine, McGill University, Montréal, QC, Canada.; Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto, Japan.; Canada Excellence Research Chair in Genomic Medicine, McGill University, Montréal, QC, Canada.; Quantitative Life Sciences Program, McGill University, Montréal, QC, Canada.; Hinda and Arthur Marcus Institute for Aging Research, Hebrew Senior Life, Boston, MA, USA.; Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.; Programs in Metabolism and Medical & Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Department of Human Genetics, McGill University, 740 Avenue Dr. Penfield, Montréal, Québec, H3A 0G1, Canada. [email protected].; Canada Excellence Research Chair in Genomic Medicine, McGill University, Montréal, QC, Canada. [email protected].; Programs in Metabolism and Medical & Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA. [email protected].

DOI: 10.1007/s11914-025-00941-2

MeSH Terms: Humans, Osteoporosis, Proteomics, Proteogenomics, Sarcopenia, Musculoskeletal Diseases, Osteoarthritis, Biomarkers, Genome-Wide Association Study