Osteoclast-stimulating Factor Interacts with the Spinal Muscular Atrophy Gene Product to Stimulate Osteoclast Formation

Noriyoshi Kurihara, Cheikh Menaa, Hidefumi Maeda, David J. Haile, Sakamuri V. Reddy

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

We have recently identified and cloned an intracellular peptide termed osteoclast-stimulating factor (OSF) that increases osteoclast (OCL) formation and bone resorption through a cellular signal transduction cascade, possibly through its interaction with c-Src or related family members. To further identify participants in the OSF signaling cascade, we used yeast two-hybrid screening with Saccharomyces cerevisiae, and we found that the 40-kDa spinal muscular atrophy disease-determining gene product, survival motor neuron (SMN), interacts with the OSF-Src homology 3 domain. Reverse transcription-polymerase chain reaction analysis of SMN mRNA expression in cells of the OCL lineage demonstrates that expression of the exon 7 splice variant of SMN is restricted to mature OCLs, whereas the unspliced transcript was expressed in OCL precursors as well as mature OCLs. Treatment of murine bone marrow cultures with conditioned media (5% (v/v)) from 293 cells transiently expressing the SMN cDNA significantly increased OCL formation, compared with treatment with conditioned media from mock-transfected cells. Furthermore, OCL-stimulatory activity by OSF or SMN was abolished by antisense constructs to SMN or OSF, respectively. These data confirm the participation of SMN in the OSF-enhanced expression of an OCL stimulator. OSF-SMN interaction may provide more insights into novel cellular signaling mechanisms that may play an important role in congenital bone fractures associated with type I spinal muscular atrophy disease.

Original languageEnglish (US)
Pages (from-to)41035-41039
Number of pages5
JournalJournal of Biological Chemistry
Volume276
Issue number44
DOIs
StatePublished - Nov 2 2001
Externally publishedYes

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Spinal Muscular Atrophy
Motor Neurons
Osteoclasts
Neurons
Genes
Bone
Muscular Diseases
Conditioned Culture Medium
Yeast
Cell signaling
Signal transduction
src Homology Domains
osteoclast stimulating factor
Polymerase chain reaction
Bone Fractures
Cell Lineage
Transcription
Survival Analysis
Bone Resorption
Reverse Transcription

ASJC Scopus subject areas

  • Biochemistry

Cite this

Osteoclast-stimulating Factor Interacts with the Spinal Muscular Atrophy Gene Product to Stimulate Osteoclast Formation. / Kurihara, Noriyoshi; Menaa, Cheikh; Maeda, Hidefumi; Haile, David J.; Reddy, Sakamuri V.

In: Journal of Biological Chemistry, Vol. 276, No. 44, 02.11.2001, p. 41035-41039.

Research output: Contribution to journalArticle

Kurihara, Noriyoshi ; Menaa, Cheikh ; Maeda, Hidefumi ; Haile, David J. ; Reddy, Sakamuri V. / Osteoclast-stimulating Factor Interacts with the Spinal Muscular Atrophy Gene Product to Stimulate Osteoclast Formation. In: Journal of Biological Chemistry. 2001 ; Vol. 276, No. 44. pp. 41035-41039.
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