Chronic arthritis leads to disturbances in the bone collagen network

Caetano-Lopes, Joana; Nery, Ana M; Canhão, Helena; Duarte, Joana; Cascão, Rita; Perpétuo, I.P.; Abdulghani, Saba; Amaral, P.M.; Sakaguchi, Shimon; Konttinen, Yrjö T.; Graça, Luís; Vaz, M. Fátima

doi:10.1186/ar2908

Cited by 29 publications

(25 citation statements)

References 12 publications

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“…Osteopenia was generalized and not purely periarticular, as demonstrated by cortical thinning of femoral midshaft ( Figure 1C). Consistent with this significant bone loss, bone from SKG mice with chronic arthritis is reported to be mechanically fragile compared with that of age-matched BALB/c mice (17). Osteopenia in arthritic SKG mice is associated with increased osteoclast activity, as demonstrated by increased serum C-terminal telopeptide of collagen type I (CTX) after arthritis induction (Supplemental Figure 1D).…”

Section: Skg Arthritis Results In Osteopenia and Erosive Bone Lesionsmentioning

confidence: 68%

Inflammatory arthritis increases mouse osteoclast precursors with myeloid suppressor function

Charles

Hsu²,

Niemi³

et al. 2012

J. Clin. Invest.

143

145

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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-

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Section: Skg Arthritis Results In Osteopenia and Erosive Bone Lesionsmentioning

confidence: 68%

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

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“…The relative distributions of mature and immature collagen were found to be equivalent in the arthritic and control groups of 5 months old SKG mice (Caetano-Lopes et al, 2009a). However, in the 8 months old SKG mice, we have observed that the ratio of the forward to backward signal was higher in arthritic animals than in control, which revealed a lower collagen density and organization (Caetano-Lopes et al, 2010). As an example, Figure 5 shows two multiphoton microscopy images from a) SKG mouse vertebrae and b) BALB/c mouse vertebrae.…”

Section: Scanning Electron Microscopy Semmentioning

confidence: 96%

“…BALB/c can be used as control for SKG mice. In five months (Caetano-Lopes et al, 2009a) and eight months (Caetano-Lopes et al, 2010) arthritic SKG mice, we have evaluated the bone structure by scanning electron microscopy and found that it was affected by the inflammatory disease. For example, the trabecular thickness was reduced from 70.91 ± 23.66 to 57.18 ± 16.78 μm in arthritic animals (CaetanoLopes et al, 2009a).…”

Section: Inflammatory Rheumatic Diseasesmentioning

confidence: 99%

“…Comparing Figures 4a) and b), respectively from control and osteoporotic mice, no particular differences can be detected with this technique, at this scale range. In an inflammatory process the lack of collagen matrix repair affects the mineral crystal deposition, which will contribute to the decreasing of mechanical strength (Caetano-Lopes et al, 2010).…”

Section: Inflammatory Rheumatic Diseasesmentioning

confidence: 99%

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Bone: A Composite Natural Material

Vaz¹,

Canhão²,

Fonseca³

2011

Advances in Composite Materials - Analysis of Natural and Man-Made Materials

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“…This phenomenon could then predispose patients to bone fragility fractures [19]. Whether bone lesions predate and cause osteoarthritis or whether cartilage disease in osteoarthritis leads in turn to bone lesions is the subject of hot debate and extensive research.…”

Section: Bone Densitometrymentioning

confidence: 99%

Nuclear medicine techniques in the assessment of alkaptonuria

Vinjamuri¹,

Ramesh²,

Jarvis³

et al. 2011

Nuclear Medicine Communications

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Alkaptonuria is a rare autosomal recessive disorder due to a lack of the enzyme homogentisate dioxygenase, leading to ochronosis, a process of accumulation of a melanin-like polymer of homogentisic acid in cartilage and other collagenous structures. Patients develop severe osteoarthropathy that resembles osteoarthritis. Although the diagnosis of alkaptonuria is not particularly challenging in view of the blue-black discolouration of visible connective tissue and the presence of homogentisic acid in urine, the natural history of alkaptonuria remains poorly understood. Patients would benefit immensely from an objective assessment of their disease status and from a clearer understanding of the pathophysiology and associated physical changes. Isotope bone scans, which are commonly used to identify the extent of involvement of bones in cancerous processes, have also been increasingly used for characterizing the extent of arthropathy in conditions such as osteoarthritis and rheumatoid arthritis. Semiquantitative scores based on the extent of involvement of joints have been used to describe the involvement of large joints in the context of symptomatic treatment for osteoarthritis. A similar semiquantitative isotope bone scan score depending on the involvement of the number of large joints in patients with alkaptonuria can be formulated and validated in a suitable cohort of patients. Bone densitometry measurement using dual-energy X-ray absorptiometry scanning is an internationally accepted tool to assess the risk and extent of osteoporosis, and is increasingly used to assess the additional fracture risk in patients with arthropathy. We believe that, currently, nuclear medicine techniques can provide useful information, which can be incorporated into disease severity scores for alkaptonuria. Once the biological basis for alkaptonuria is better understood, it is feasible that nuclear medicine techniques of even greater sensitivity and specificity can be developed, thereby taking advantage of the vast advances in the fields of radiochemistry, radiopharmacy, positron emission tomography-computed tomography and positron emission tomography-magnetic resonance imaging scanning.

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Chronic arthritis leads to disturbances in the bone collagen network

Cited by 29 publications

References 12 publications

Inflammatory arthritis increases mouse osteoclast precursors with myeloid suppressor function

Inflammatory arthritis increases mouse osteoclast precursors with myeloid suppressor function

Bone: A Composite Natural Material

Nuclear medicine techniques in the assessment of alkaptonuria

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