TY - JOUR
T1 - CCN Proteins as Matricellular Regulators of Bone in Aging and Disease
AU - Abdul-Azees, Parveez Ahamed
AU - Rajesh, Rahul
AU - Block, Travis J.
AU - Dean, David D.
AU - Yeh, Chih Ko
AU - Capitano, Maegan
AU - Kacena, Melissa
AU - Chen, Xiao Dong
AU - Marinković, Miloš
N1 - Publisher Copyright:
© This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2025.
PY - 2025/12
Y1 - 2025/12
N2 - Purpose 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. Summary: 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.
AB - Purpose 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. Summary: 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.
KW - Aging bone marrow
KW - Extracellular matrix
KW - Matricellular signaling
KW - Mesenchymal stem cells
KW - Osteoblasts
KW - Osteoclasts
UR - https://www.scopus.com/pages/publications/105005656815
UR - https://www.scopus.com/pages/publications/105005656815#tab=citedBy
U2 - 10.1007/s11914-025-00915-4
DO - 10.1007/s11914-025-00915-4
M3 - Review article
C2 - 40407982
AN - SCOPUS:105005656815
SN - 1544-1873
VL - 23
JO - Current Osteoporosis Reports
JF - Current Osteoporosis Reports
IS - 1
M1 - 23
ER -