<p>As reported, miR-422a holds promise as an underlying biomarker of postmenopausal osteoporosis (PMOP). The objective of this article was to clarify the definite influences of exosomal miR-422a derived from bone mesenchymal stem cells (BMSCs) on angiogenesis and osteogenesis. Through flow cytometry, the BMSCs isolated from OP patients and the exosomes derived from the BMSCs (BMSCs-Exos) were identified. miR-422a level was tested through RT-qPCR. The effects of miR-422a on the angiogenesis of HUVECs cells and the osteogenic differentiation of hFOB1.19 cells were investigated by angiogenesis assay, alizarin red staining, and Alkaline phosphatase (ALP) activity. The levels of proteins relevant to osteogenesis were unraveled through Western blot. Subsequently, dual-luciferase reporter gene assays were implemented to confirm the targeting relationship between miR-422a and Kallikrein-related peptidase 4 (KLK4). Additionally, a bilateral ovariectomy model in mice was established to uncover the involvement of miR-422a in BMSCs-Exos in the angiogenesis and osteogenesis of mice. We found that miR-422a was over-expressed notably in BMSCs-Exos, while KLK4 under-expressed, miR-422a negatively controlled KLK4. BMSCs-Exos dampened the angiogenesis from HUVECs, the formation of mineralized nodules from hFOB1.19 cells, declined ALP activity and osteogenesis protein levels. Knockdown miR-422a attenuated the interference of BMSCs-Exos with angiogenesis and osteogenesis, but overexpression miR-422a enhanced this interference. Overexpression KLK4 attenuated the inhibitory impact of BMSCs-Exos on angiogenesis and osteogenesis. Moreover, the miR-422a in BMSCs-Exos hindered the angiogenesis and osteogenesis in mice. In conclusion, miR-422a in BMSCs-Exos declined the KLK4 expression, thereby suppressed the angiogenesis from HUVECs and the osteogenesis of hFOB1.19 cells.</p>