The gelatinases, matrix metalloproteinases 2 and 9, play individual roles in skeleton development

MMP2 loss leads to defective parturition and severe dystocia in mice

“…Thus, impaired pelvis of the mmp2 -/pregnant female along with the wider skull observed in the mmp2 -/fetuses, can be one of the possible causes for cephalopelvic disproportion resulting in dystocia in these mice, as was previously reported in women [45,46,50]. Moreover, as we found that while some P0 mmp2 -/newborns have significantly wider skull, others have milder or no skull defect [21], this can explain why some fetuses are able to be expelled from the uterus while others get physically stacked and die. Finally, the use of knockout mice for different MMPs throughout the years has allowed the investigation into their role in various aspects of physiology, including reproductive function.…”

“…Concomitantly, we have previously found that during development, both MMP2 and MMP9 are required for executing the migration of the unique population of neural crest cells (NCCs) in both chick and mouse embryos, and each MMP compensates for the loss of the other [18]; see also Duong and Erickson 2004 and Monsonego-Ornan et al, 2012 [19,20]. On the other hand, in our recent study on skeleton development, we found that each gelatinase has an individual and unique role; while MMP2 was found to have a role in intramembranous ossification affecting the development of the skull and the cortices, MMP9 was demonstrated to have a role in endochondral ossification affecting the longitudinal growth of the skeleton, and the overall body length [21]. Hence, their redundant or individual activities are highly context dependent.…”

“…CPD occurs when there is mismatch between the size of the fetal head and size of the maternal pelvis, resulting in “failure to progress” in labor for mechanical reasons; if untreated, the consequence is obstructed labor that can endanger the lives of both mother and fetus [45,46]. Hence, an additional possible mechanism for the abnormal parturition and dystocia can be related to the defective skeleton of mmp2 -/- mice [21]. We have recently uncovered the role of MMP2 and MMP9 in skeleton development and found that, while MMP9 participates in endochondral ossification process and its loss affects the length of long bones, MMP2 participates in intramembranous ossification process and its loss results in shorter but wider skulls of the neonates together with thinner and less mineralized cortices [21].…”

“…Mmp2 -/- [25,26], mmp9 -/- [27], dKO (mmp2 -/- mmp9 -/- ) [21] and wild-type (WT) C57BL/6J mice were used. WT and mmp9 -/- mice were purchased from Harlan laboratories (Rehovot, Israel), while mmp2 -/- mice were provided from Martignetti Lab (Mount Sinai School of Medicine, NY, USA).…”

“…WT and mmp9 -/- mice were purchased from Harlan laboratories (Rehovot, Israel), while mmp2 -/- mice were provided from Martignetti Lab (Mount Sinai School of Medicine, NY, USA). dKO mice were generated at our lab, as detailed in Kalev-Altman 2020, and Kalev-Altman 2022 [18,21]. Additional genotypes (mmp2 +/- , mmp9 +/- , mmp2 +/- mmp9 +/- , mmp2 -/- mmp9 +/- , mmp2 +/- mmp9 -/- ) were generated at the lab.…”