Sphingomyelin phosphodiesterase 3 (SMPD3)， a lipid-metabolizing enzyme present in bone and cartilage， has important roles in the developing skeleton. We previously showed that SMPD3 deficiency results in delayed extracellular matrix (ECM) mineralization and severe skeletal deformities in an inducible knockout mouse model， ; mice， in which was ablated in -expressing chondrocytes and osteoblasts during early skeletogenesis. However， as shown in the current study， ablation of postnatally in 3-month-old ; mice resulted in only a mild bone mineralization defect. Interestingly， though， there was a marked increase of unmineralized osteoid in the fractured tibiae of 3-month-old ; mice. As was th... More
Sphingomyelin phosphodiesterase 3 (SMPD3)， a lipid-metabolizing enzyme present in bone and cartilage， has important roles in the developing skeleton. We previously showed that SMPD3 deficiency results in delayed extracellular matrix (ECM) mineralization and severe skeletal deformities in an inducible knockout mouse model， ; mice， in which was ablated in -expressing chondrocytes and osteoblasts during early skeletogenesis. However， as shown in the current study， ablation of postnatally in 3-month-old ; mice resulted in only a mild bone mineralization defect. Interestingly， though， there was a marked increase of unmineralized osteoid in the fractured tibiae of 3-month-old ; mice. As was the case in the embryonic bones， we also observed impaired chondrocyte apoptosis at the fracture sites of ; mice. We further examined how expression is regulated in ATDC5 chondrogenic cells by two major regulators of chondrogenesis， bone morphogenetic protein 2 (BMP-2) and PTHrP. Our data show that BMP-2 positively regulates expression via p38 mitogen-activated protein kinase. Taken together， our findings show that SMPD3 plays a significant role in ECM mineralization and chondrocyte apoptosis during fracture healing. Furthermore， our gene expression analyses suggest that BMP-2 and PTHrP exert opposing effects on the regulation of expression in chondrocytes.
