Abdul‑Azees, Parveez AhamedRajesh, RahulBlock, Travis J.Dean, David D.Yeh, Chih‑KoCapitano, MaeganKacena, MelissaChen, Xiao‑DongMarinković, Miloš2025-06-162025-06-162025-05-23Abdul-Azees PA, Rajesh R, Block TJ, et al. CCN Proteins as Matricellular Regulators of Bone in Aging and Disease. Curr Osteoporos Rep. 2025;23(1):23. Published 2025 May 23. doi:10.1007/s11914-025-00915-4https://hdl.handle.net/1805/48715Purpose of review: This review explores the role of cell communication network (CCN) proteins in regulating skeletal physiology, aging, and disease, particularly within the context of balanced bone remodeling. Recent findings: Recent conceptualization of paracrine and endocrine networks in bone marrow as a form of osteoimmunological crosstalk suggests a significant role for matricellular signaling in regulating bone homeostasis. As multifunctional adapters of cell-matrix interactions, CCNs are emerging as a focal point for parathyroid hormone (PTH) signaling and regulation of the RANKL/RANK/OPG axis in skeletal aging. Altered bone marrow CCN expression creates a permissive environment for accelerated postmenopausal bone loss and may contribute to the pathogenesis of osteoporosis and other diseases related to skeletal aging. CCNs modulate fundamental signaling mechanisms in bone development, homeostasis and repair. During aging, dysregulation of CCNs may negatively affect skeletal health and contribute to disease progression. As a result, CCNs may constitute promising therapeutic targets for improving and maintaining aging bone health.en-USAttribution 4.0 InternationalAging bone marrowMatricellular signalingExtracellular matrixMesenchymal stem cellsOsteoblastsOsteoclastsArticle