Microtubule assembly affects bone mass by regulating both osteoblast and osteoclast functions: Stathmin deficiency produces an osteopenic phenotype in mice

Hongbin Liu, Rongrong Zhang, Seon Yle Ko, Babatunde O. Oyajobi, Christopher J. Papasian, Hong Wen Deng, Shujun Zhang, Ming Zhao

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Cytoskeleton microtubules regulate various cell signaling pathways that are involved in bone cell function. We recently reported that inhibition of microtubule assembly by microtubule-targeting drugs stimulates osteoblast differentiation and bone formation. To further elucidate the role of microtubules in bone homeostasis, we characterized the skeletal phenotype of mice null for stathmin, an endogenous protein that inhibits microtubule assembly. In vivo micro-computed tomography (μCT) and histology revealed that stathmin deficiency results in a significant reduction of bone mass in adult mice concurrent with decreased osteoblast and increased osteoclast numbers in bone tissues. Phenotypic analyses of primary calvarial cells and bone marrow cells showed that stathmin deficiency inhibited osteoblast differentiation and induced osteoclast formation. In vitro overexpression studies showed that increased stathmin levels enhanced osteogenic differentiation of preosteoblast MC3T3-E1cells and mouse bone marrow-derived cells and attenuated osteoclast formation from osteoclast precursor Raw264.7cells and bone marrow cells. Results of immunofluorescent studies indicated that overexpression of stathmin disrupted radial microtubule filaments, whereas deficiency of stathmin stabilized the microtubule network structure in these bone cells. In addition, microtubule-targeting drugs that inhibit microtubule assembly and induce osteoblast differentiation lost these effects in the absence of stathmin. Collectively, these results suggest that stathmin, which alters microtubule dynamics, plays an essential role in maintenance of postnatal bone mass by regulating both osteoblast and osteoclast functions in bone.

Original languageEnglish (US)
Pages (from-to)2052-2067
Number of pages16
JournalJournal of Bone and Mineral Research
Volume26
Issue number9
DOIs
StatePublished - Sep 2011

Keywords

  • BONE MASS
  • MICROTUBULE
  • OSTEOBLAST
  • OSTEOCLAST
  • STATHMIN

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

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