Deletion of the nuclear localization sequence and C-terminus of parathyroid hormone-related protein decreases osteogenesis and chondrogenesis but increases adipogenesis and myogenesis in murine bone marrow stromal cells.

The N-terminus of parathyroid hormone-related protein regulates bone marrow stromal cell differentiation. We hypothesized that the nuclear localization sequence and C-terminus are involved. MicroRNA and gene expression analyses were performed on bone marrow stromal cells from mice lacking the nuclear localization sequence and C-terminus ( ) and age-matched controls. Differentiation assays with microRNA, cytochemical/histologic/morphologic, protein, and gene expression analyses were performed. bone marrow stromal cells are anti-osteochondrogenic, pro-adipogenic, and pro-myogenic, expressing more , , , , and but less , , , , and (⩽ 0.024). osteoblasts had less mineralization, osteocalcin, , , , and (⩽ 0.029). produced more adipocytes, , and , but less (⩽ 0.042). cartilage pellets were smaller with less and , but greater (⩽ 0.024). produced more myocytes, , and (⩽ 0.021). MicroRNA changes supported these findings. In conclusion, the nuclear localization sequence and C-terminus are pro-osteochondrogenic, anti-adipogenic, and anti-myogenic.