# CCN Proteins as Matricellular Regulators of Bone in Aging and Disease

## TL;DR

This paper reviews how CCN proteins influence bone health, aging, and diseases like osteoporosis by regulating cell and matrix interactions.

## Contribution

The paper highlights CCN proteins as key regulators of bone remodeling and potential therapeutic targets for skeletal aging.

## Key findings

- CCN proteins are central to paracrine/endocrine signaling in bone marrow and osteoimmunological crosstalk.
- Dysregulation of CCNs during aging may lead to bone loss and osteoporosis.
- CCNs modulate signaling pathways like RANKL/RANK/OPG and PTH, making them potential therapeutic targets.

## Abstract

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 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.