KIAA1199 deficiency enhances skeletal stem cell differentiation to osteoblasts and promotes bone regeneration
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KIAA1199 deficiency enhances skeletal stem cell differentiation to osteoblasts and promotes bone regeneration. / Chen, Li; Shi, Kaikai; Ditzel, Nicholas; Qiu, Weimin; Figeac, Florence; Nielsen, Louise Himmelstrup Dreyer; Tencerova, Michaela; Kowal, Justyna Magdalena; Ding, Ming; Andreasen, Christina Møller; Andersen, Thomas Levin; Kassem, Moustapha.
I: Nature Communications, Bind 14, Nr. 1, 2016, 2023.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - KIAA1199 deficiency enhances skeletal stem cell differentiation to osteoblasts and promotes bone regeneration
AU - Chen, Li
AU - Shi, Kaikai
AU - Ditzel, Nicholas
AU - Qiu, Weimin
AU - Figeac, Florence
AU - Nielsen, Louise Himmelstrup Dreyer
AU - Tencerova, Michaela
AU - Kowal, Justyna Magdalena
AU - Ding, Ming
AU - Andreasen, Christina Møller
AU - Andersen, Thomas Levin
AU - Kassem, Moustapha
N1 - Publisher Copyright: © 2023. The Author(s).
PY - 2023
Y1 - 2023
N2 - Upon transplantation, skeletal stem cells (also known as bone marrow stromal or mesenchymal stem cells) can regulate bone regeneration by producing secreted factors. Here, we identify KIAA1199 as a bone marrow stromal cell-secreted factor in vitro and in vivo. KIAA1199 plasma levels of patients positively correlate with osteoporotic fracture risk and expression levels of KIAA1199 in patient bone marrow stromal cells negatively correlates with their osteogenic differentiation potential. KIAA1199-deficient bone marrow stromal cells exhibit enhanced osteoblast differentiation in vitro and ectopic bone formation in vivo. Consistently, KIAA1199 knockout mice display increased bone mass and biomechanical strength, as well as an increased bone formation rate. They also exhibit accelerated healing of surgically generated bone defects and are protected from ovariectomy-induced bone loss. Mechanistically, KIAA1199 regulates osteogenesis by inhibiting the production of osteopontin by osteoblasts, via integrin-mediated AKT and ERK-MAPK intracellular signaling. Thus, KIAA1199 is a regulator of osteoblast differentiation and bone regeneration and could be targeted for the treatment or management of low bone mass conditions.
AB - Upon transplantation, skeletal stem cells (also known as bone marrow stromal or mesenchymal stem cells) can regulate bone regeneration by producing secreted factors. Here, we identify KIAA1199 as a bone marrow stromal cell-secreted factor in vitro and in vivo. KIAA1199 plasma levels of patients positively correlate with osteoporotic fracture risk and expression levels of KIAA1199 in patient bone marrow stromal cells negatively correlates with their osteogenic differentiation potential. KIAA1199-deficient bone marrow stromal cells exhibit enhanced osteoblast differentiation in vitro and ectopic bone formation in vivo. Consistently, KIAA1199 knockout mice display increased bone mass and biomechanical strength, as well as an increased bone formation rate. They also exhibit accelerated healing of surgically generated bone defects and are protected from ovariectomy-induced bone loss. Mechanistically, KIAA1199 regulates osteogenesis by inhibiting the production of osteopontin by osteoblasts, via integrin-mediated AKT and ERK-MAPK intracellular signaling. Thus, KIAA1199 is a regulator of osteoblast differentiation and bone regeneration and could be targeted for the treatment or management of low bone mass conditions.
U2 - 10.1038/s41467-023-37651-1
DO - 10.1038/s41467-023-37651-1
M3 - Journal article
C2 - 37037828
AN - SCOPUS:85152095371
VL - 14
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 2016
ER -
ID: 343294471