甲状旁腺激素相关蛋白的N端调节骨髓基质细胞分化。我们假设涉及核定位序列和C末端。对来自缺乏核定位序列和C-末端(PthrpΔ/Δ)的小鼠的骨髓基质细胞和年龄匹配的对照进行MicroRNA和基因表达分析。用microRNA进行分化分析,细胞化学/组织学/形态学,蛋白质,并进行基因表达分析。PthrpΔ/Δ骨髓基质细胞是抗骨软骨,促脂肪生成,和促肌源性,表达更多的Klf4,Gsk-3β,Lif,Ct-1和microRNA-434,但β-catenin较少,Igf-1Taz,Osm,和microRNA-22(p﹤0.024)。PthrpΔ/Δ成骨细胞矿化较少,骨钙蛋白,Runx2,Osx,Igf-1和瘦素(p﹤0.029)。PthrpΔ/Δ产生更多的脂肪细胞,pparγ,和aP2,但Lpl较少(p﹤0.042)。PthrpΔ/Δ软骨颗粒较小,Sox9和Pth1r较少,但更大的Col2a1(p﹤0.024)。PthrpΔ/Δ产生更多的肌细胞,Des,和Myog(p﹤0.021)。MicroRNA的变化支持了这些发现。总之,核定位序列和C端是前骨软骨,抗脂肪,和抗肌源性。
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 (PthrpΔ/Δ ) and age-matched controls. Differentiation assays with microRNA, cytochemical/histologic/morphologic, protein, and gene expression analyses were performed. PthrpΔ/Δ bone marrow stromal cells are anti-osteochondrogenic, pro-adipogenic, and pro-myogenic, expressing more Klf4, Gsk-3β, Lif, Ct-1, and microRNA-434 but less β-catenin, Igf-1, Taz, Osm, and microRNA-22 (p ⩽ 0.024). PthrpΔ/Δ osteoblasts 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, but greater Col2a1 (p ⩽ 0.024). PthrpΔ/Δ produced more myocytes, Des, and Myog (p ⩽ 0.021). MicroRNA changes supported these findings. In conclusion, the nuclear localization sequence and C-terminus are pro-osteochondrogenic, anti-adipogenic, and anti-myogenic.