Osteoblast-osteoclast interactions

Abstract

Bone homeostasis depends on the resorption of bones by osteoclasts and formation of bones by the osteoblasts. Imbalance of this tightly coupled process can cause diseases such as osteoporosis. Thus, the mechanisms that regulate communication between osteoclasts and osteoblasts are critical to bone cell biology. It has been shown that osteoblasts and osteoclasts can communicate with each other through direct cell-cell contact, cytokines, and extracellular matrix interaction. Osteoblasts can affect osteoclast formation, differentiation, or apoptosis through several pathways, such as OPG/RANKL/RANK, RANKL/LGR4/RANK, Ephrin2/ephB4, and Fas/FasL pathways. Conversely, osteoclasts also influence formation of bones by osteoblasts via the d2 isoform of the vacuolar (H+) ATPase (v-ATPase) V0 domain (Atp6v0d2), complement component 3a, semaphorin 4D or microRNAs. In addition, cytokines released from the resorbed bone matrix, such as TGF-β and IGF-1, also affect the activity of osteoblasts. Drugs could be developed by enhancing or restricting some of these interactions. Several reviews have been performed on the osteoblast-osteoclast communication. However, few reviews have shown the research advances in the recent years. In this review, we summarized the current knowledge on osteoblast-osteoclast communication.

Keywords: Bone; bone remodeling; communication; osteoblast; osteoclast.

Figure 1

The schematic presentation of osteoblast–osteoclast interactions. Osteoblasts can enhanced the proliferation, differentiation, survival, apoptosis or fusion by macrophage colonystimulating factor (M-CSF)/C-Fms, receptor activator of nuclear factor-κB ligand (RANKL), lysophosphatidic acid/lysophosphatidic acid receptor (LPA/LPAR) and Fas/FasL (FADD, Fas-associated death domain). Osteoblasts also inhibit (⊥) the differentiation, proliferation or survival of osteoclast by osteoprotegerin (OPG), RANKL/LGR4 and Sema3A/Nrp1. Osteoclasts can promote osteoblasts differentiation by Complement Component 3a (CC3)/CC3 receptor (CC3R) and ephrinB2. D2 isoform of vacuolar (H+) ATPase (v-ATPase) V0 domain (Atp6v0d2), Semaphorin 4D, Sclerostin, MicroRNAs (miR-214 and miR-214-3p) or exsomes from osteoclast can inhibit (⊥) the differentiation or activity of osteoblast. There are also bidirectional interactions (EphB4-ephrinB2) between osteoblasts and osteoclasts.