Kindlin-2 modulates PTH1R to regulate bone mass and PTH actions in bone

To investigation the role of PTH and Kindlin-2 in bone development, we performed single-cell RNA-sequencing. From Con-veh, Con-PTH, cKO-veh, cKO-PTH, we profiled more than 20k single cells, including multi-potent mesenchymal stromal cells (MSC), osteoprogenitors, osteoblasts, chondrocytes, fibroblasts, endothelial cells, smooth muscle cells, skeletal muscle cells, pericytes, and schwann cells. We found proportion of part of these cells were significant altered by PTH or Kindlin-2 loss, especially for MSC, osteoblast, chondrocyte, and fibroblast. Transcriptomic analysis revealed gene expression was dramatically regulated by PTH or Kindlin-2 loss. 3-month-old Kindlin-2f/f (control, n=6) and Dmp1-Cre; Kindlin-2f/f (cKO, n=6) mice were treated with or without PTH daily continuously for 28d. Mice were sacrificed after the last PTH injection. Non-hematopoietic cells from bone marrow were extracted for single-cell RNA-sequencing