Chondrocytes are well adapted to hypoxia and produce more functional extracellular matrix in low oxygen environments in vitro . In our previous study, methyltransferase SET domain containing (SETD)7 regulated chondrocyte activity in hypoxic conditions. However, the precise association between SETD7 and chondrocyte differentiation under low oxygen partial pressure remains unclear. The association between SETD7 and chondrocyte differentiation was studied by silencing SETD7 in chondrocytes in vitro . The results showed that the silencing of SETD7 in ATDC5 cells inhibited the Hippo signaling pathway, decreased Yes-associated protein (YAP) phosphorylation and increased the levels of YAP and hypoxia inducible factor-1α (HIF-1α) in the nucleus. YAP combined with HIF-1α to form a complex that promoted the expression of genes involved in chondrogenic differentiation and the glycolytic pathway. Thus, SETD7 inhibited chondrocyte differentiation and glycolysis via the Hippo signaling pathway. The present study demonstrated that SETD7 was a potential molecular target that maintained the chondrocyte phenotype during cartilage tissue engineering and cartilage-associated disease.

The pathological characteristics of osteoarthritis are cartilage matrix degradation, chondrocytes apoptosis, and low‐grade inflammation of the joint. Recent studies have shown that blood vessels grow from the subchondral bone to the articular cartilage. However, the relationship among inflammation, angiogenesis, and chondrocyte apoptosis is still unclear. We found that chondrocytes could secrete chemokines and VEGF to promote the migration of vascular endothelial cells in response to TNF‐α stimulation. The invasion of blood vessels leads to increased oxygen tension in the local environment, which increased the expression of SETD7 in chondrocytes by activating the JAK‐STAT5 pathway. The bond of phosphorylated STAT5 and the specific locus in the promoter of SETD7 directly increased the transcription of SETD7. On the one hand, SETD7‐regulated chemokine expression by forming a positive loop; on the other hand, SETD7‐mediated chondrocyte apoptosis by inhibiting the nuclear localization of HIF‐1α. In this study, we discovered a novel function of chondrocytes as mediators of inflammation and angiogenesis. Our study demonstrates that SETD7 is a potential molecular target to prevent OA development and progression.

Macrophages are known to modulate the osteogenic environment of bone regeneration elicited by biological bone grafts. Alteration in certain chemical components tends to affect macrophages polarization. Comparatively to hydroxyapatite (HAp), carbonate hydroxyapatite (CHA) consists of 7.4 (wt%) carbonate ions and more closely resembles the mineral content of bone. It remains unknown whether CHA scaffolds or HA scaffolds have better osteogenic properties. In this study, we fabricated PCL/SF scaffold, PCL/SF/HAp scaffold and PCL/SF/CHA scaffold using the electrospinning technique. Despite comparable mechanical properties, the PCL/SF/CHA scaffold exhibited better osteogenic properties than the PCL/SF/HAp scaffold. Although no significant differences were observed between the two scaffolds for promoting osteoblast differentiation in vitro, the PCL/SF/CHA group appeared to be more effective at promoting bone regeneration in cranial defects in vivo. The PCL/SF/CHA scaffold was found to promote macrophage polarization toward M2 via activating the JAK/STAT5 pathway which caused a pro-osteogenic microenvironment to facilitate osteoblast differentiation. The results of this study indicated a higher potential of CHA to substitute HAp in the production of bone scaffolds for better bone regeneration.