Aging negatively impacts the ability of megakaryocytes to stimulate osteoblast proliferation and bone mass

Kevin A. Maupin, Evan R. Himes, Artur P. Plett, Hui Lin Chua, Pratibha Singh, Joydeep Ghosh, Safa F. Mohamad, Irushi Abeysekera, Alexa Fisher, Carol Sampson, Jung Min Hong, Paul Childress, Marta Alvarez, Edward Srour, Angela Bruzzaniti, Louis Pelus, Christie Orschell, Melissa Kacena

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)452-459
Number of pages8
JournalBone
Volume127
DOIs
StatePublished - Oct 1 2019

Fingerprint

Megakaryocytes
Osteoblasts
Bone and Bones
Coculture Techniques
Transplantation
Cell Transplantation
Osteogenesis
Transforming Growth Factor beta
Down-Regulation

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 journalArticle

Maupin, KA, Himes, ER, Plett, AP, Chua, HL, Singh, P, Ghosh, J, Mohamad, SF, Abeysekera, I, Fisher, A, Sampson, C, Hong, JM, Childress, P, Alvarez, M, Srour, E, Bruzzaniti, A, Pelus, L, Orschell, C & Kacena, M 2019, 'Aging negatively impacts the ability of megakaryocytes to stimulate osteoblast proliferation and bone mass', Bone, vol. 127, pp. 452-459. https://doi.org/10.1016/j.bone.2019.07.010
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. / Aging negatively impacts the ability of megakaryocytes to stimulate osteoblast proliferation and bone mass. In: Bone. 2019 ; Vol. 127. pp. 452-459.
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