Functional Differences Between Osteoclasts and Osteoclast-like Cells Differentiated from Peripheral Blood Mononuclear Cells in Patients with Rheumatoid Arthritis

Kazuhiro Yokota¹, Yoshimi Aizaki ¹, Shinya Tanaka ², Kojiro Sato ³, Yasuto Araki ¹, Noritsune Kouzu ⁴, Yuho Kadono ², Hiromi Oda ⁵ and Toshihide Mimura ¹, ¹Department of Rheumatology and Applied Immunology, Faculty of Medicine, Saitama Medical University, Saitama, Japan, ²Department of Orthopaedic Surgery, Saitama Medical University, Saitama, Japan, ³Division of Rheumatology and Clinical Immunology, Department of Medicine, Jichi Medical University, Tochigi, Japan, ⁴Medical Kouzu orthopedic and Yachiyo radiation center, Chiba, Japan, ⁵Department of Orthopedic Surgery, Faculty of Medicine, Saitama Medical University, Saitama, Japan

Meeting: 2019 ACR/ARP Annual Meeting

Keywords: inflammatory cytokines and matrix metalloproteinase (MMP), joint destruction, osteoclastogenesis, Rheumatoid arthritis (RA)

Session Information

Date: Tuesday, November 12, 2019

Title: Osteoarthritis & Joint Biology – Basic Science Poster

Session Type: Poster Session (Tuesday)

Session Time: 9:00AM-11:00AM

Background/Purpose: Osteoclasts (OCs) are giant multinucleated cells formed from precursors of the monocyte/macrophage lineage and are believe to play a major role in the bone destruction associated with rheumatoid arthritis (RA). Previously, we have reported that osteoclast-like cells (OLCs) are differentiated from mouse bone marrow macrophages stimulated with TNFα and IL-6; they show bone resorption activity both in vitro and in vivo. The purpose of the present study is to investigate the functional differences between OCs and OLCs differentiated from peripheral blood mononuclear cells (PBMCs) from patients with RA or healthy controls (HCs).

Methods: PBMCs and CD14⁺ monocytes from 9 RA patients and/or HCs were stimulated with RANKL or TNFα and IL-6. The number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells (OCs/OLCs) and bone resorption activity were assessed. Quantitative RT-PCR was used to measure the mRNA expression levels of cathepsin K and matrix metalloproteinases (MMPs). The relationship between the number of OCs/OLCs and the modified total Sharp score (mTSS) or whole-body bone mineral density (BMD) was also examined.

Results: The number of OCs/OLCs differentiated from PBMCs in RA patients was significantly higher than that in HCs (RA OCs, 30.7±7.3 vs. HCs OCs, 10.0±4.0, p< 0.01; RA OLCs, 16.0±6.1 vs. HCs OLCs, 2.3±0.7, p< 0.01). These cells showed bone resorption activity on dentin slices. Moreover, CD14+ monocytes-differentiated OCs and OLCs showed significantly increased expression of cathepsin K mRNA compared with osteoclast precursors (OCPs) (OCs 9.4±3.5-fold, OLCs 2.3±0.5-fold vs. OCPs 1.0±0.0-fold, p< 0.01, respectively). In addition, the expression levels of MMP-3 mRNA was significantly higher in OLCs than in OCs and OCPs (OLCs, 35.7±12.8-fold vs. OCs 2.8±0.5-fold, OCPs 1.0±0.0-fold, p< 0.01, respectively). The number of OLCs differentiated from PBMCs in RA patients was significantly positively correlated with the mTSS, erosion score, and joint space narrowing score (r=0.82, r=0.79, and r=0.68, respectively, p< 0.05), while the number of OCs was not. On the other hand, the number of OCs was significantly negatively correlated with the whole-body BMD (r=-0.67, p< 0.05), while the number of OLCs was not.

Conclusion: Our results demonstrated that the PBMCs of RA patients showed a higher OC/OLC differentiation potential than those from HCs. The bone resorption activity of PBMC-differentiated OLCs could likely have a potential role in the joint destruction, whereas OC activity plays an important role in the development of osteoporosis in RA patients. OLCs could form a subpopulation of OCs; possibly, this is one of the functional differences between OLCs and conventional OCs.

Disclosure: K. Yokota, None; Y. Aizaki, None; S. Tanaka, None; K. Sato, None; Y. Araki, None; N. Kouzu, None; Y. Kadono, None; H. Oda, None; T. Mimura, None.

To cite this abstract in AMA style:

Yokota K, Aizaki Y, Tanaka S, Sato K, Araki Y, Kouzu N, Kadono Y, Oda H, Mimura T. Functional Differences Between Osteoclasts and Osteoclast-like Cells Differentiated from Peripheral Blood Mononuclear Cells in Patients with Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/functional-differences-between-osteoclasts-and-osteoclast-like-cells-differentiated-from-peripheral-blood-mononuclear-cells-in-patients-with-rheumatoid-arthritis/. Accessed .

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