Bone Cell Communication Factors Provide a New Therapeutic Strategy for Osteoporosis

Abstract

Bone homeostasis is strictly regulated by the balance between bone resorption by osteoclasts and bone formation by osteoblasts. Many studies have shown that osteoclasts affect osteoblasts, and vice versa, through diffusible paracrine factors, cell-cell contact, and cell-bone matrix interactions to achieve the correct balance between osteoclastic and osteoblastic activities in the basic multicellular unit (BMU). The strict regulation that occurs during bone remodeling hinders the long-term use of the currently available antiresorptive agents and anabolic agents for the treatment of osteoporosis. To overcome these limitations, it is necessary to develop novel agents that simultaneously inhibit bone resorption, promote bone formation, and decouple resorption from formation. Therefore, a more detailed understanding of the mechanisms involved in osteoclast-osteoblast communication during bone remodeling is necessary.

Keywords: Cell Communication; Osteoblasts; Osteoclasts; Osteoporosis; Paracrine Communication.

FIG. 1. The dual roles of bone cell communication factors during bone remodeling. The forward Receptor activator of nuclear factor kappa-B ligand (RANKL) signaling pathway originating from osteoblasts is known to induce osteoclast differentiation, and reverse RANKL signaling from osteoclasts also induces osteoblast formation. Several in vitro and in vivo studies have shown that some bone cell communication factors, such as semaphorin 3A (SEMA3A), slit guidance ligand 3 (SLIT3), and collagen triple-helix repeat-containing 1 (CTHRC1), stimulate bone formation while suppressing bone resorption, and other factors, such as semaphorin 4D (SEMA4D) and sclerostin, inhibit bone formation while increasing bone formation. The roles of these bone cell communication factors in both osteoclasts and osteoblasts offer a new strategy for the development of bone disease therapies.