Substance P modulates bone remodeling properties of murine osteoblasts and osteoclasts.

Abstract:

:Clinical observations suggest neuronal control of bone remodeling. Sensory nerve fibers innervating bone, bone marrow and periosteum signal via neurotransmitters including substance P (SP). In previous studies we observed impaired biomechanical and structural bone parameters in tachykinin (Tac) 1-deficient mice lacking SP. Here, we aim to specify effects of SP on metabolic parameters of bone marrow macrophage (BMM)/osteoclast cultures and osteoblasts isolated from Tac1-deficient and wildtype (WT) mice. We demonstrated endogenous SP production and secretion in WT bone cells. Absence of SP reduced bone resorption rate, as we found reduced numbers of precursor cells (BMM) and multinucleated osteoclasts and measured reduced cathepsin K activity in Tac1-/- BMM/osteoclast cultures. However, this might partly be compensated by reduced apoptosis rate and increased fusion potential of Tac1-/- precursor cells to enlarged "super" osteoclasts. Contrarily, increased ALP enzyme activity and apoptosis rate during early osteoblast differentiation accelerated osteogenesis and cell death in the absence of SP together with reduced ALP activity of Tac1-/- osteoblasts during late osteogenic differentiation resulting in reduced bone formation at later stages. Therefore, we suggest that absence of SP presumably results in a slight reduction of bone resorption rate but concomitantly in a critical reduction of bone formation and mineralization rate.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Niedermair T,Schirner S,Seebröker R,Straub RH,Grässel S

doi

10.1038/s41598-018-27432-y

subject

Has Abstract

pub_date

2018-06-15 00:00:00

pages

9199

issue

1

issn

2045-2322

pii

10.1038/s41598-018-27432-y

journal_volume

8

pub_type

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