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The N-terminus of parathyroid hormone–related protein regulatesbone marrow stromal cell differentiation. We hypothesized that the nuclear localizationsequence and C-terminus are involved. MicroRNA and gene expression analyses wereperformed on bone marrow stromal cells from mice lacking the nuclear localizationsequence and C-terminus (PthrpΔ/Δ) and age-matched controls. Differentiation assays withmicroRNA, cytochemical/histologic/morphologic, protein, and gene expression analyseswere performed. PthrpΔ/Δ bone marrow stromal cells are anti-osteochondrogenic,pro-adipogenic, and pro-myogenic, expressing more Klf4, Gsk-3β, Lif, Ct-1, andmicroRNA-434 but less β-catenin, Igf-1, Taz, Osm, and microRNA-22 (p ⩽ 0.024). PthrpΔ/Δosteoblasts had less mineralization, osteocalcin, Runx2, Osx, Igf-1, and leptin(p ⩽ 0.029). PthrpΔ/Δ produced more adipocytes, Pparγ, and aP2, but less Lpl(p ⩽ 0.042). PthrpΔ/Δ cartilage pellets were smaller with less Sox9 and Pth1r, butgreater Col2a1 (p ⩽ 0.024). PthrpΔ/Δ produced more myocytes, Des, and Myog (p ⩽ 0.021).MicroRNA changes supported these findings. In conclusion, the nuclear localizationsequence and C-terminus are pro-osteochondrogenic, anti-adipogenic, andanti-myogenic

journal of tissue engineering

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