Chondrocyte biology is a hot topic, because osteoarthritis (OA) is a serious problem in an aging society, but there are no fundamental therapeutic drugs. This Special Issue aimed to collect the recent progress in the molecular aspects of chondrocyte proliferation, differentiation, and death and the pathogenesis of OA and rheumatoid arthritis (RA). In the comprehensive review of skeletal development, Shawn A. Hallett and colleagues emphasized skeletal stem cells, which are a population of chondrocytes in the resting zone expressing parathyroid hormone-related protein (PTHrP). These cells have an ability of self-renewal and give rise to columnar chondrocytes. Further, these cells transdifferentiate into osteoblasts and bone marrow stromal cells during skeletal development. Lineage-tracing experiments revealed the transdifferentiation of terminally differentiated chondrocytes into osteoblasts and bone marrow stromal cells and identified PTHrP-expressing skeletal stem cells and transient mesenchymal precursors (borderline chondrocytes)[1]. Hironori Hojo and Shinsuke Ohba reviewed the gene regulatory mechanisms addressed by next-generation sequencer analyses, which included histone modification, binding of transcription factors and cofactors, and the topological organization of chromatin, focusing on Sox family genes (Sox9, Sox5, and Sox6) in the transcriptional regulation of chondrocyte-distinct genes. For example, the binding of Sox9 and AP-1 or Gli to the enhancers and their interaction with the target genes regulate chondrogenesis [2]. Satoshi Kubota and colleagues described the basal mechanisms of genome editing by retrotransposons and their involvement in skeletal development. For example, the mutation of Poc1a, which encodes a component of centrosome, by long interspersed nuclear element-1 (LINE-1)-mediated retrogene transposition leads to the craniofacial and skeletal abnormalities through the impaired polarity of growth plate chondrocytes. Short-legged dogs were created by the addition of extra fibroblast growth factor 4 (FGF4) cDNA, which is caused by LINE-1. The integration of Alu retrotransposon to ZBTB38 is involved in the determination of height in humans [3].

Mitsuhiro Hoshijima and colleagues showed the interaction between CCN2 and Rab14, their colocalization in the cytosol, and the reduction in the extracellular proteoglycan by dominantnegative Rab14 and suggested that this association may be involved in the trafficking of proteoglycancontaining vesicles in chondrocytes [4]. Our group published two reports related to chondrocyte proliferation. Antxr1/Tem8 is a receptor for anthrax, and its mutation causes GAPO syndrome, which is characterized by growth retardation (G), alopecia (A), pseudoanodontia (P), and optic atrophy (O). Qing Jiang and colleagues showed that Antxr1 expression is directly regulated by Runx2; it plays an important role in chondrocyte proliferation, and the overexpression of Antxr1 increases chondrocyte proliferation but causes chondrocyte apoptosis accompanied by matrix mineralization [5]. Hck is a member of the Src tyrosine kinase family. Viviane KS Kawata Matsuura and colleagues showed that Hck is highly expressed in chondrocytes, and its expression is directly regulated by Runx2 and that the expression of a constitutively active form of Hck (HckCA) disorganized the growth plate but markedly increased chondrocyte proliferation without enhancing apoptosis. Further, HckCA activated the Wnt and hedgehog signaling pathways, indicating that chondrocyte proliferation is increased by