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

Academic Article

Abstract

  • 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 (Pthrp ) and age-matched controls. Differentiation assays with microRNA, cytochemical/histologic/morphologic, protein, and gene expression analyses were performed. Pthrp 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). Pthrp osteoblasts had less mineralization, osteocalcin, Runx2, Osx, Igf-1, and leptin (p ⩽ 0.029). Pthrp produced more adipocytes, Pparγ, and aP2, but less Lpl (p ⩽ 0.042). Pthrp cartilage pellets were smaller with less Sox9 and Pth1r, but greater Col2a1 (p ⩽ 0.024). Pthrp 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. Δ/Δ Δ/Δ Δ/Δ Δ/Δ Δ/Δ Δ/Δ
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    Author List

  • Hildreth BE; Hernon KM; Dirksen WP; Leong J; Supsavhad W; Boyaka PN; Rosol TJ; Toribio RE
  • Volume

  • 6