Figure 4. Baseline age-related differences in ECM/MMPs and TGF-beta signaling were detected in both the proteome and transcriptome. COMPBIO analysis of (A) the proteome and (B) the transcriptome indicated baseline changes in ECM/MMPs. (C) At the protein level, the top 10 themes included Lamin/Progeria, ECM/MMPs, and ER-Associated Degradation. (D) At the RNA level, the top 10 themes included ECM/MMPs, Dendrites, and TGF-beta signaling. Examination of age-related differences in individual (E) proteins and (F) genes related to TGF-beta signaling and perilacunar remodeling (PLR) showed reduced TGF-beta levels but higher Mmp13. (G) RNA ISH for Tgfb2 showed predominant expression in osteocytes. (H) Periosteal Tgfb2 expression was minimal in young-adult bone and even lower in old bone. (I) Over half of osteocytes (OCY) within cortical bone expressed Tgfb2, and this percentage was lower in old bone. (J) The areal density of Tgfb2-positive osteocytes was about half in old versus young bone.