S100 Calcium-Binding Protein P Secreted from Megakaryocytes Promotes Osteoclast Maturation.

Seung-Hoon Lee,Hye Jung Ihn,Eui Kyun Park,Jung-Eun Kim

doi:10.3390/ijms22116129

Seung-Hoon Lee, Hye Jung Ihn + Show 2 more

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https://doi.org/10.3390/ijms22116129

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Abstract

Megakaryocytes (MKs) differentiate from hematopoietic stem cells and produce platelets at the final stage of differentiation. MKs directly interact with bone cells during bone remodeling. However, whether MKs are involved in regulating bone metabolism through indirect regulatory effects on bone cells is unclear. Here, we observed increased osteoclast differentiation of bone marrow-derived macrophages (BMMs) cultured in MK-cultured conditioned medium (MK CM), suggesting that this medium contains factors secreted from MKs that affect osteoclastogenesis. To identify the MK-secreted factor, DNA microarray analysis of the human leukemia cell line K562 and MKs was performed, and S100 calcium-binding protein P (S100P) was selected as a candidate gene affecting osteoclast differentiation. S100P was more highly expressed in MKs than in K562 cells, and showed higher levels in MK CM than in K562-cultured conditioned medium. In BMMs cultured in the presence of recombinant human S100P protein, osteoclast differentiation was promoted and marker gene expression was increased. The resorption area was significantly larger in S100P protein-treated osteoclasts, demonstrating enhanced resorption activity. Overall, S100P secreted from MKs promotes osteoclast differentiation and resorption activity, suggesting that MKs indirectly regulate osteoclast differentiation and activity through the paracrine action of S100P.

Highlights

Published: 7 June 2021Megakaryocytes (MKs) are cells with large lobulated nuclei that differentiate from hematopoietic stem cells in the bone marrow [1,2]
K562 cells were differentiated into mature MKs in phorbol 12-myristate 13-acetate (PMA)-supplemented medium for 7 days [26]; differentiation was determined by morphological changes, such as an increased nuclear/cytoplasmic ratio, large and multilobulated nuclei, and strong adhesion
Based on several reports that MKs may indirectly contribute to skeletal homeostasis [12,27], we investigated the effects of MK-cultured conditioned medium (MK CM) on osteoclast differentiation

Summary

Introduction

Published: 7 June 2021Megakaryocytes (MKs) are cells with large lobulated nuclei that differentiate from hematopoietic stem cells in the bone marrow [1,2]. Several studies have shown that MKs and platelets are involved in bone tissue healing. When bone tissue undergoes fractures, platelets move to the fracture site to minimize bleeding and contribute to the healing process by secreting growth factors and cytokines, indicating that platelets are required to mitigate the inflammatory response at the fracture site and to heal the bone fracture [7]. Clinical studies showed that platelet-rich plasma increases the healing rate and reduces the healing duration and infection incidence [8,9]. The specific MKs and platelets directly involved in bone metabolism are unclear. A direct interaction has been detected between MKs and osteoblasts, with MKs increasing osteoblast proliferation and bone mass, suggesting an anabolic role for MKs in skeletal homeostasis [10,11].

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