Papp-a2 modulates development of cranial cartilage and angiogenesis in zebrafish embryos

Mutations in pregnancy‐associated plasma protein A2 cause short stature due to low IGF ‐I availability

“…PAPP‐A2 is responsible for the proteolysis of IGFBP‐5 during pregnancy resulting in increased fIGF‐I (Yan et al , ), but how this affects fetal growth and development in normal individuals and in our subjects is unknown. Lack of PAPP‐A2 led to decreased length of the mandible, skull, femur, pelvic girdle, and tailbone in mice (Christians et al , ) and severely reduced cranial cartilages in zebrafish (Kjaer‐Sorensen et al , ). Our subjects had small chins, long thin fingers, thin femurs and moderate microcephaly.…”

Pregnancy-Associated Plasma Protein (PAPP)-A2 in Physiology and Disease

“…The importance of Pappa2 in bone and joint development is emphasized by the demonstration of its expression in the epiphyseal cartilage of the acetabulum and femoral head of the hip joints of rats at different perinatal stages [ 64 ], as well as in the epiphysis and metaphysis, including osteoblasts, of the femur and tibia of 19-day-old mice [ 65 ]. Analysis of Pappa2 expression has also been performed in zebrafish embryos, larvae and adults, with adult tissues such as bone, muscle, eye, brain, gill, kidney, gastrointestinal tract, ovary and testis shown to have higher expression levels than other tissues [ 66 ]. Together, these findings confirm the physiological importance of PAPP-A2 in the promotion of placental, fetal and postnatal growth, and support the hypothesis that PAPP-A2 may act as a local tissue-specific modulator of IGF1 bioavailability by cleavage of ternary complexes containing IGFBP3 or IGFBP5 and IGFALS.…”

“…Analysis of a morpholino-mediated Pappa2 KD zebrafish embryo model (50% and 43% overall sequence identity to human PAPP-A2 and PAPP-A , respectively, and conserved proteolytic activity in human IGFBP3 and IGFBP5) suggested that Pappa2 actions in normal growth and development may also be exerted through non-proteolytic modulation of Notch signaling [ 66 ]. While IGFBP-independent mechanisms of PAPP-A2 cannot be excluded, overall results to date indicate that the modulation of IGF1 bioavailability through its release from ternary and binary complexes should be further investigated in a tissue, sex and age-specific manner.…”

“…Moreover, when the effects of whole body and osteoblast-specific Pappa2 deletion were compared, only mandible dimensions and femur length showed significant differences, emphasizing the importance of PAPP-A2 at the tissue level. Studies of the Pappa2 KD zebrafish model suggested that Pappa2 function is required for normal development of Meckel’s and cranial cartilages [ 66 ].…”

Associations of plasma PAPP-A2 and genetic variations with salt sensitivity, blood pressure changes and hypertension incidence in Chinese adults

“…Pregnancy-associated plasma protein-A2 (PAPP-A2, also known as pappalysin-2) shares 45% of its residues with PAPP-A, and is the only homolog of PAPP-A in the vertebrate genome [11,12]. In humans, single-cell transcriptome analysis confirmed the expression of PAPP-A2 in the development of fetal kidney [13].…”