TY - JOUR
T1 - Runx2 promotes both osteoblastogenesis and novel osteoclastogenic signals in ST2 mesenchymal progenitor cells
AU - Baniwal, S. K.
AU - Shah, P. K.
AU - Shi, Y.
AU - Haduong, J. H.
AU - DeClerck, Y. A.
AU - Gabet, Y.
AU - Frenkel, B.
N1 - Funding Information:
We thank USC’s Dr. Elizabeth Lowler (Children’s Hospital Los Angeles) for the pSLIK system. This work was supported by NIH grants DK071122, DK071122S1, and AR047052 to BF, who holds the J. Harold and Edna L. LaBriola Chair in Genetic Orthopedic Research at USC. SKB was partially supported by a postdoctoral Innovative Chapter Research Award and YG was partially supported by a Meyer Young Investigator Fellowship, both from the Arthritis Foundation Southern California Chapter.
PY - 2012/4
Y1 - 2012/4
N2 - Summary We profiled the global gene expression of a bone marrow-derived mesenchymal pluripotent cell line in response to Runx2 expression. Besides osteoblast differentiation, Runx2 promoted the osteoclastogenesis of co-cultured splenocytes. This was attributable to the upregulation of many novel osteoclastogenic genes and the downregulation of antiosteoclastogenic genes. Introduction In addition to being a master regulator for osteoblast differentiation, Runx2 controls osteoblast-driven osteoclastogenesis. Previous studies profiling gene expression during osteoblast differentiation had limited focus on Runx2 or paid little attention to its role in mediating osteoblast-driven osteoclastogenesis. Methods ST2/Rx2dox, a bone marrow-derived mesenchymal pluripotent cell line that expresses Runx2 in response to Doxycycline (Dox), was used to profile Runx2- induced gene expression changes. Runx2-induced osteoblast differentiation was assessed based on alkaline phosphatase staining and expression of classical marker genes. Osteoclastogenic potential was evaluated by TRAP staining of osteoclasts that differentiated from primary murine splenocytes co-cultured with the ST2/Rx2dox cells. The BeadChip™ platform (Illumina) was used to interrogate genome-wide expression changes in ST2/Rx2dox cultures after treatment with Dox or vehicle for 24 or 48 h. Expression of selected genes was also measured by RT-qPCR. Results Dox-mediated Runx2 induction in ST2 cells stimulated their own differentiation along the osteoblast lineage and the differentiation of co-cultured splenocytes into osteoclasts. The latter was attributable to the stimulation of osteoclastogenic genes such as Sema7a, Ltc4s, Efnb1, Apcdd1, and Tnc as well as the inhibition of antiosteoclastogenic genes such as Tnfrsf11b (OPG), Sema3a, Slco2b1, Ogn, Clec2d (Ocil), Il1rn, and Rspo2. Conclusion Direct control of osteoblast differentiation and concomitant indirect control of osteoclast differentiation, both through the activity of Runx2 in pre-osteoblasts, constitute a novel mechanism of coordination with a potential crucial role in coupling bone formation and resorption.
AB - Summary We profiled the global gene expression of a bone marrow-derived mesenchymal pluripotent cell line in response to Runx2 expression. Besides osteoblast differentiation, Runx2 promoted the osteoclastogenesis of co-cultured splenocytes. This was attributable to the upregulation of many novel osteoclastogenic genes and the downregulation of antiosteoclastogenic genes. Introduction In addition to being a master regulator for osteoblast differentiation, Runx2 controls osteoblast-driven osteoclastogenesis. Previous studies profiling gene expression during osteoblast differentiation had limited focus on Runx2 or paid little attention to its role in mediating osteoblast-driven osteoclastogenesis. Methods ST2/Rx2dox, a bone marrow-derived mesenchymal pluripotent cell line that expresses Runx2 in response to Doxycycline (Dox), was used to profile Runx2- induced gene expression changes. Runx2-induced osteoblast differentiation was assessed based on alkaline phosphatase staining and expression of classical marker genes. Osteoclastogenic potential was evaluated by TRAP staining of osteoclasts that differentiated from primary murine splenocytes co-cultured with the ST2/Rx2dox cells. The BeadChip™ platform (Illumina) was used to interrogate genome-wide expression changes in ST2/Rx2dox cultures after treatment with Dox or vehicle for 24 or 48 h. Expression of selected genes was also measured by RT-qPCR. Results Dox-mediated Runx2 induction in ST2 cells stimulated their own differentiation along the osteoblast lineage and the differentiation of co-cultured splenocytes into osteoclasts. The latter was attributable to the stimulation of osteoclastogenic genes such as Sema7a, Ltc4s, Efnb1, Apcdd1, and Tnc as well as the inhibition of antiosteoclastogenic genes such as Tnfrsf11b (OPG), Sema3a, Slco2b1, Ogn, Clec2d (Ocil), Il1rn, and Rspo2. Conclusion Direct control of osteoblast differentiation and concomitant indirect control of osteoclast differentiation, both through the activity of Runx2 in pre-osteoblasts, constitute a novel mechanism of coordination with a potential crucial role in coupling bone formation and resorption.
KW - Co-culture
KW - Microarray
KW - Osteoblast
KW - Osteoclast
KW - Runx2
UR - http://www.scopus.com/inward/record.url?scp=84861754133&partnerID=8YFLogxK
U2 - 10.1007/s00198-011-1728-5
DO - 10.1007/s00198-011-1728-5
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AN - SCOPUS:84861754133
SN - 0937-941X
VL - 23
SP - 1399
EP - 1413
JO - Osteoporosis International
JF - Osteoporosis International
IS - 4
ER -