Abstract
Osteoblast number and activity decreases with aging, contributing to the age-associated decline of bone mass, but the mechanisms underlying changes in osteoblast activity are not well understood. Here, we show that the age-associated bone loss critically depends on impairment of the ability of megakaryocytes (MKs) to support osteoblast proliferation. Co-culture of osteoblast precursors with young MKs is known to increase osteoblast proliferation and bone formation. However, co-culture of osteoblast precursors with aged MKs resulted in significantly fewer osteoblasts compared to co-culture with young MKs, and this was associated with the downregulation of transforming growth factor beta. In addition, the ability of MKs to increase bone mass was attenuated during aging as transplantation of GATA1low/low hematopoietic donor cells (which have elevated MKs/MK precursors) from young mice resulted in an increase in bone mass of recipient mice compared to transplantation of young wild-type donor cells, whereas transplantation of GATA1low/low donor cells from old mice failed to enhance bone mass in recipient mice compared to transplantation of old wild-type donor cells. These findings suggest that the preservation or restoration of the MK-mediated induction of osteoblast proliferation during aging may hold the potential to prevent age-associated bone loss and resulting fractures.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 452-459 |
| Number of pages | 8 |
| Journal | Bone |
| Volume | 127 |
| DOIs | |
| State | Published - Oct 1 2019 |
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Keywords
- Aging
- Bone loss
- Bone mass
- Megakaryocytes
- Osteoblasts
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Physiology
- Histology
Cite this
Aging negatively impacts the ability of megakaryocytes to stimulate osteoblast proliferation and bone mass. / Maupin, Kevin A.; Himes, Evan R.; Plett, Artur P.; Chua, Hui Lin; Singh, Pratibha; Ghosh, Joydeep; Mohamad, Safa F.; Abeysekera, Irushi; Fisher, Alexa; Sampson, Carol; Hong, Jung Min; Childress, Paul; Alvarez, Marta; Srour, Edward; Bruzzaniti, Angela; Pelus, Louis; Orschell, Christie; Kacena, Melissa.
In: Bone, Vol. 127, 01.10.2019, p. 452-459.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Aging negatively impacts the ability of megakaryocytes to stimulate osteoblast proliferation and bone mass
AU - Maupin, Kevin A.
AU - Himes, Evan R.
AU - Plett, Artur P.
AU - Chua, Hui Lin
AU - Singh, Pratibha
AU - Ghosh, Joydeep
AU - Mohamad, Safa F.
AU - Abeysekera, Irushi
AU - Fisher, Alexa
AU - Sampson, Carol
AU - Hong, Jung Min
AU - Childress, Paul
AU - Alvarez, Marta
AU - Srour, Edward
AU - Bruzzaniti, Angela
AU - Pelus, Louis
AU - Orschell, Christie
AU - Kacena, Melissa
PY - 2019/10/1
Y1 - 2019/10/1
N2 - Osteoblast number and activity decreases with aging, contributing to the age-associated decline of bone mass, but the mechanisms underlying changes in osteoblast activity are not well understood. Here, we show that the age-associated bone loss critically depends on impairment of the ability of megakaryocytes (MKs) to support osteoblast proliferation. Co-culture of osteoblast precursors with young MKs is known to increase osteoblast proliferation and bone formation. However, co-culture of osteoblast precursors with aged MKs resulted in significantly fewer osteoblasts compared to co-culture with young MKs, and this was associated with the downregulation of transforming growth factor beta. In addition, the ability of MKs to increase bone mass was attenuated during aging as transplantation of GATA1low/low hematopoietic donor cells (which have elevated MKs/MK precursors) from young mice resulted in an increase in bone mass of recipient mice compared to transplantation of young wild-type donor cells, whereas transplantation of GATA1low/low donor cells from old mice failed to enhance bone mass in recipient mice compared to transplantation of old wild-type donor cells. These findings suggest that the preservation or restoration of the MK-mediated induction of osteoblast proliferation during aging may hold the potential to prevent age-associated bone loss and resulting fractures.
AB - Osteoblast number and activity decreases with aging, contributing to the age-associated decline of bone mass, but the mechanisms underlying changes in osteoblast activity are not well understood. Here, we show that the age-associated bone loss critically depends on impairment of the ability of megakaryocytes (MKs) to support osteoblast proliferation. Co-culture of osteoblast precursors with young MKs is known to increase osteoblast proliferation and bone formation. However, co-culture of osteoblast precursors with aged MKs resulted in significantly fewer osteoblasts compared to co-culture with young MKs, and this was associated with the downregulation of transforming growth factor beta. In addition, the ability of MKs to increase bone mass was attenuated during aging as transplantation of GATA1low/low hematopoietic donor cells (which have elevated MKs/MK precursors) from young mice resulted in an increase in bone mass of recipient mice compared to transplantation of young wild-type donor cells, whereas transplantation of GATA1low/low donor cells from old mice failed to enhance bone mass in recipient mice compared to transplantation of old wild-type donor cells. These findings suggest that the preservation or restoration of the MK-mediated induction of osteoblast proliferation during aging may hold the potential to prevent age-associated bone loss and resulting fractures.
KW - Aging
KW - Bone loss
KW - Bone mass
KW - Megakaryocytes
KW - Osteoblasts
UR - http://www.scopus.com/inward/record.url?scp=85069721739&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85069721739&partnerID=8YFLogxK
U2 - 10.1016/j.bone.2019.07.010
DO - 10.1016/j.bone.2019.07.010
M3 - Article
VL - 127
SP - 452
EP - 459
JO - Bone
JF - Bone
SN - 8756-3282
ER -