Proteomics Reveals Age-Related Changes in Mouse Bone Formation

A new research paper was published on the cover of Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science), Volume 16, Issue 19 on October 12, 2024, entitled, "A proteomics approach to study mouse long bones: examining baseline differences and mechanical loading-induced bone formation in young-adult and old mice."

As noted in the abstract, bone mass declines with age, and the anabolic effects of skeletal loading decrease. While much research has focused on gene transcription, how bone ages and loses its mechanoresponsiveness at the protein level remains unclear.

In their paper, researchers Christopher J. Chermside-Scabbo, John T. Shuster, Petra Erdmann-Gilmore, Eric Tycksen, Qiang Zhang, R. Reid Townsend, and Matthew J. Silva from Washington University School of Medicine and Washington University in St. Louis, Missouri, describe how they developed a novel proteomics approach and conducted paired mass spectrometry and RNA-seq analyses on tibias from young-adult (5-month) and old (22-month) mice.

The researchers report the first correlation estimate between the bone proteome and transcriptome (Spearman ρ = 0.40). While this is consistent with findings from other tissues, it suggests that only a relatively low amount of variation in protein levels is explained by variation in transcript levels.

Of the 71 shared targets that differed with age, eight were associated with bone mineral density in previous GWAS, including the understudied targets Asrgl1 and Timp2. Using complementary RNA in situ hybridization, the researchers confirmed that Asrgl1 and Timp2 showed reduced expression in osteoblasts/osteocytes in aged bones. Additionally, they found evidence of reduced TGF-beta signaling with aging, particularly Tgfb2. The researchers also identified proteomic changes following mechanical loading, noting that at the protein level, bone differed more with age than with loading, and aged bone exhibited fewer loading-induced changes.

"Overall, our findings underscore the need for complementary protein-level assays in skeletal biology research."