Endogenous Collagenases Regulate Osteoclast Fusion.

Hyo Jeong Kim,Youngkyun Lee

doi:10.3390/biom10050705

Hyo Jeong Kim, Youngkyun Lee

Open Access

https://doi.org/10.3390/biom10050705

Copy DOI

Journal: Biomolecules	Publication Date: May 1, 2020
Citations: 5	License type: CC BY 4.0

Affiliation: Kyungpook National University

Abstract

The precise regulation of osteoclast differentiation and function is crucial for the maintenance of healthy bone. Despite several reports of collagenase expression in bone tissues, the precise isoform expression as well as the role in osteoclasts are still unclear. In the present report, the expression of matrix metalloprotease (MMP)8 and MMP13 was confirmed in mouse bone marrow macrophage osteoclast precursors. The mRNA and protein expressions of both collagenases were significantly reduced by receptor activator of nuclear factor κB ligand (RANKL) stimulation. Notably, either inhibition of MMP expression by siRNA or treatment of cells with collagenase inhibitor Ro 32-3555 significantly augmented osteoclast fusion and resorption activity without affecting the osteoclast number. The inhibition of collagenase by Ro 32-3555 increased the expression of osteoclast fusion genes, Atp6v0d2 and Dcstamp, without affecting nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) protein expression. The enhanced osteoclast fusion by collagenase inhibition appears to be mediated through an extracellular signal regulated kinase (ERK)-dependent pathway. Collectively, these data provide novel information on the regulation of osteoclast fusion process.

Highlights

Osteoclasts are sole bone-resorbing cells found in the skeletons of higher vertebrates originated from the macrophage/monocyte lineage of hematopoietic stem cells [1]
In an effort to delineate the roles of endogenous collagenases during osteoclastogenesis, the expression of MMP1, MMP8, and MMP13 was examined in Bone marrow macrophages (BMMs) treated with macrophage-colony stimulating factor (M-CSF) and RANKL (Figure 1A)
The expression levels of both MMP8 and MMP13 were highest at day 0 and significantly decreased during osteoclast differentiation

Summary

Introduction

Osteoclasts are sole bone-resorbing cells found in the skeletons of higher vertebrates originated from the macrophage/monocyte lineage of hematopoietic stem cells [1]. The unbalance in the bone remodeling, in many cases uncontrolled osteoclast differentiation and activation, often leads to pathological skeletal conditions seen in osteoporosis, rheumatoid arthritis, and periodontitis [3,4,5]. The macrophage-colony stimulating factor (M-CSF) furnished by bone microenvironment supports the survival of osteoclast precursors, while receptor activator of nuclear factor κB ligand (RANKL) induces their differentiation. In early phase of osteoclastogenesis, the precursor cells are committed by multiple RANKL-dependent signaling events including mitogen-activated protein kinases (MAPKs), nuclear factor κB (NFκB), and nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), the key transcription factor for osteoclastogenesis [6,7,8]. The committed mononuclear osteoclasts fuse to form mature, fully functional multinuclear osteoclasts. The information on the regulation of this later phase of osteoclastogenesis is considerably lacking, compared with the vast amount of knowledge regarding early signaling events [9,10]

Methods

Results

Conclusion