Role of cyclin-dependent kinase (Cdk)6 in osteoblast, osteoclast, and chondrocyte differentiation and its potential as a target of bone regenerative medicine

Abstract

In the oral and maxillofacial region, conditions such as bone fracture, trauma-induced bone or cartilage defects, and tumor or birth defects are common, and it is necessary to elucidate the molecular mechanisms that control the differentiation of cells to establish new treatment strategies for these conditions. Therefore, numerous studies have investigated the role or involvement of factors that are thought to be crucial for differentiation of cells, including cell cycle factors, transcription factors, and growth factors. One of these types of factors, the cell cycle factors, critically influence the differentiation of cells, since a temporal arrest in the G1 phase of the cell cycle or withdrawal from the cell cycle is thought to be a prerequisite for cell differentiation. In a previous attempt to identify cell cycle factor(s) controlling the commitment for differentiation of cells, we discovered that cyclin-dependent kinase (Cdk)6, one of the G1 cell cycle factors, is a critical regulator of the differentiation efficiency of osteoblasts, osteoclasts, and chondrocytes. In addition, individual groups have also reported the importance of Cdk6 in differentiation in other cell types. Herein, we review the role of Cdk6 in differentiation of cells with a particular focus on osteoblast, osteoclast, and chondrocyte differentiation and discuss the potential of Cdk6 as a target of bone regenerative medicine.