Infliximab inhibits bone resorption by circulating osteoclast precursor cells in patients with rheumatoid arthritis and ankylosing spondylitis

Gengenbacher, Michael; Sebald, H.; Villiger, Peter M.; Hofstetter, Willy; Seitz, Michael

doi:10.1136/ard.2007.076711

Cited by 59 publications

(43 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several studies suggest that OCPs are also altered by inflammation. Increased circulating OCPs can be detected in psoriatic arthritis and RA patients (20,48). In the hTNF-α-Tg murine arthritis model, both BM and peripheral blood OCPs were increased in arthritic mice, as we see in the present study.…”

Section: Discussionsupporting

confidence: 74%

Inflammatory arthritis increases mouse osteoclast precursors with myeloid suppressor function

Charles

Hsu²,

Niemi³

et al. 2012

J. Clin. Invest.

143

145

View full text Add to dashboard Cite

Increased osteoclastic bone resorption leads to periarticular erosions and systemic osteoporosis in RA patients. Although a great deal is known about how osteoclasts differentiate from precursors and resorb bone, the identity of an osteoclast precursor (OCP) population in vivo and its regulatory role in RA remains elusive. Here, we report the identification of a CD11b -/lo Ly6C hi BM population with OCP activity in vitro and in vivo. These cells, which can be distinguished from previously characterized precursors in the myeloid lineage, display features of both M1 and M2 monocytes and expand in inflammatory arthritis models. Surprisingly, in one mouse model of RA (adoptive transfer of SKG arthritis), cotransfer of OCP with SKG CD4 + T cells diminished inflammatory arthritis. Similar to monocytic myeloid-derived suppressor cells (M-MDSCs), OCPs suppressed CD4 + and CD8 + T cell proliferation in vitro through the production of NO. This study identifies a BM myeloid precursor population with osteoclastic and T cell-suppressive activity that is expanded in inflammatory arthritis. Therapeutic strategies that prevent the development of OCPs into mature bone-resorbing cells could simultaneously prevent bone resorption and generate an antiinflammatory milieu in the RA joint. IntroductionOsteoclasts are the primary bone-resorbing cell and are essential for physiologic bone remodeling. In the absence of either RANK or its ligand RANKL, the essential receptor-ligand pair for osteoclast differentiation and survival, mice lack osteoclasts and have severe osteopetrosis with absence of tooth eruption (1-3). Osteoclasts are myeloid lineage cells that also require M-CSF for differentiation and survival (4, 5). Osteoclasts can be cultured in vitro from BM, peripheral blood, or spleen cells in the presence of M-CSF and RANKL. Although BM CD11b -/lo CD115 + CD117 + cells are enriched in osteoclast differentiation activity (6, 7), the cell-surface phenotype and biology of the BM osteoclast precursor (OCP) and its relationship to other myeloid lineages has not been characterized in depth.The common monocyte DC precursor (MDP) was described as having the cell-surface phenotype CD11b -CD115 + CD117 int (8), and differentiation of monocytes and DCs from MDPs has been intensely studied (reviewed in ref. 9). It is likely that MDPs can also differentiate into osteoclasts, as a population with a similar surface phenotype is capable of differentiation into osteoclasts, macrophages, or DCs, depending on cytokine conditions (6, 10). Recent work confirmed the primary BM OCPs as CD11b -/lo CD115 + CD117 + , although CD117 -cells were also able to differentiate into osteoclasts less efficiently (6, 7). BM OCPs in the human TNFA Tg (hTNF-α-Tg) mouse were identified by others as characterized by the markers CD11b + and Gr-1 -, using the 1A-8 antibody that is specific for the granulocyte Ly6G receptor, the main component of the Gr-1 epitope (11). Recent studies have identified a circulating quiescent lin-

show abstract

Section: Discussionsupporting

confidence: 74%

Inflammatory arthritis increases mouse osteoclast precursors with myeloid suppressor function

Charles

Hsu²,

Niemi³

et al. 2012

J. Clin. Invest.

143

145

View full text Add to dashboard Cite

show abstract

“…Unique for the multinucleated osteoclast is its ability to dissolve mineral and proteins of mineralized tissue. In some studies, the signals of unstimulated PBMCs proved to be sufficient to generate bone resorbing osteoclasts [7,15,22,26], whereas in other studies M-CSF and RANKL were required for bone resorption [9,10,20,21].…”

Section: Osteoclast Formation From Pbmcs From Patients With Bone-lytimentioning

confidence: 95%

“…Since the pioneering study of Ritchlin et al [7], osteoclast formation from PBMCs from rheumatic diseases [7][8][9][10][11][12][13], osteoporosis [14][15][16][17][18], periodontitis [19,20], chronic liver disease with osteopenia [21] and osteolytic cancers [22][23][24][25] was investigated. Typically, osteoclast formation of PBMCs from these patients was compared with healthy controls, either unstimulated (in the absence of macrophage colony forming factor (M-CSF) and RANKL) or stimulated (in the presence of M-CSF and RANKL).…”

Section: Osteoclast Formation From Pbmcs From Patients With Bone-lytimentioning

confidence: 99%

Osteoclast Formation from Peripheral Blood of Patients with Bone-lytic Diseases

Vries

Everts

2009

Clinic Rev Bone Miner Metab

View full text Add to dashboard Cite

Recent literature indicates that osteoclast formation in vitro from peripheral blood of patients with diseases associated with bone loss such as rheumatoid arthritis, osteoporosis, periodontitis and bone metastatic cancer may occur spontaneously being independent of addition of osteoclast formation stimulating factors such as macrophage colony forming factor (M-CSF) and receptor activator of NFjB ligand (RANKL). This could provide important clues to our understanding on how osteoclast precursors are primed within the circulation whilst commuting to the site of ultimate osteoclast differentiation. When comparing the various bone-lytic diseases, the common view emerges that accessory cells, such as T-and B-lymphocytes provide osteoclastogenesis stimulating factors. The roles of B-and T-cells in providing osteoclastogenesis-positive signals such RANKL, TNF-a and IL-7 are discussed. Immune cells present in the circulation may play an important role in preparing the osteoclast precursor for its ultimate destiny, contributing to the bone resorbing multinucleated cell at the required bone site.

show abstract

“…With regard to possible systemic changes resulting from TNF blockade, such neutralization can also lead to a reduction in osteoclast precursors (i.e., a monocyte subpopulation) in the blood of patients with RA or psoriatic arthritis (78,79) and to a reduction in peripheral blood monocyte numbers in RA (80) and Crohn's disease (81). These findings are consistent with the data indicating that TNF administration can promote myelopoiesis (82) and mobilization of cycling osteoclast precursors into peripheral blood from bone marrow (83).…”

Section: Cytokine Blockade Tnf Il-1 and Il-6mentioning

confidence: 99%

The dynamics of macrophage lineage populations in inflammatory and autoimmune diseases

Hamilton¹,

Tak²

2009

Arthritis & Rheumatism

197

183

View full text Add to dashboard Cite

Infliximab inhibits bone resorption by circulating osteoclast precursor cells in patients with rheumatoid arthritis and ankylosing spondylitis

Abstract: These results provide an explanation on the cellular level for the anticatabolic effect of TNF neutralisation on bone. The variation in the kinetics of bone resorption by the OCPs in patients with RA and AS suggests disease-specific differences in the type or in the preactivation of OCPs.

Cited by 59 publications

References 19 publications

Inflammatory arthritis increases mouse osteoclast precursors with myeloid suppressor function

Inflammatory arthritis increases mouse osteoclast precursors with myeloid suppressor function

Osteoclast Formation from Peripheral Blood of Patients with Bone-lytic Diseases

The dynamics of macrophage lineage populations in inflammatory and autoimmune diseases

Contact Info

Product

Resources

About