PHEX and infection: In a three-dimensional co-culture model simulating biomaterial-associated infection (BAI), Giraldo-Osorno et al.93 found that M1 macrophages inhibit osteogenesis by downregulating osteogenesis-related genes in osteocytes, such as OCN and phosphate-regulating neutral endopeptidase on chromosome X (PHEX), upregulating anti-mineralization genes like matrix extracellular phosphoglycoprotein (MEPE), and increasing the expression of the pro-osteoclastogenic factor RANKL.