Sex-specific hormonal rescue of bone growth in PAPPA2-deficient mice

Aims: deficient mouse model of growth impairment, and to identify the associated signalling pathways. Methods: ) mice of both sexes received daily treatment with rhGH, rhIGF1, or rhPAPP-A2 from postnatal day (PND) 5 to PND 35. The IGF1 system, bone remodelling factors, cannabinoid receptors, and intracellular signalling were analyzed in bone. Results: deficiency and hormone therapy were associated with numerous sex-specific differences in bone IGF1 binding, bone remodelling, cannabinoid receptors, and signal transducer and activator of transcription 3 (STAT3) signalling. Conclusion: These findings support rhPAPP-A2 as a promising therapeutic candidate for mitigating postnatal bone growth retardation by increasing bone formation and reducing resorption through cannabinoid receptor modulation in a female-specific manner.