Expression patterns and function of chromatin protein HMGB2 during mesenchymal stem cell differentiation

Noboru Taniguchi,Yasuhiko Kawakami,Martin Lotz,Beatriz Caramés

doi:10.1186/ar3669

Noboru Taniguchi, Yasuhiko Kawakami + Show 2 more

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https://doi.org/10.1186/ar3669

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Abstract

The superficial zone (SZ) of articular cartilage is critical in maintaining tissue function and homeostasis and represents the site of the earliest changes in osteoarthritis (OA). The expression of chromatin protein HMGB2 is restricted to the SZ, which contains cells expressing mesenchymal stem cell (MSC) markers [1]. Aging-related loss of HMGB2 and gene deletion are associated with reduced SZ cellularity and early onset OA [2]. This study addressed HMGB2 expression patterns in MSC and its role during differentiation. HMGB2 was detected at higher levels in human MSC as compared to human articular chondrocytes and its expression declined during chondrogenic differentiation of MSC (Figure (Figure1).1). Lentiviral HMGB2 transduction of MSC suppressed chondrogenesis as reflected by an inhibition of Col2a1 and Col10a1 expression. Conversely, in bone marrow MSC from Hmgb2-/- mice, Col10a1 was more strongly expressed than in wildtype MSC. This is consistent with in vivo results from mouse growth plates showing that Hmgb2 is expressed in proliferating and prehypertrophic zones but not in hypertrophic cartilage where Col10a1 is strongly expressed. Osteogenesis was also accelerated in Hmgb2-/- MSC. The expression of Runx2, which plays a major role in late stage chondrocyte differentiation, was enhanced in Hmgb2-/- MSC and HMGB2 negatively regulated the stimulatory effect of Wnt/β-catenin signaling on the Runx2 proximal promoter. Figure 1 HMGB2 expression during chondrogenesis of human MSC. Immunohistochemistry shows that HMGB2 is expressed at days 1 and 3, but that expression is reduced at days 7, 14 upon induction of chondrogenesis. SO: safranin O staining. These results demonstrate that HMGB2 expression is inversely correlated with the differentiation status of MSC and that HMGB2 suppresses chondrogenic differentiation. The aging-related loss of HMGB2 in articular cartilage may represent a mechanism responsible for the decline in adult cartilage stem cell populations.

Highlights

Acute isolated neurological syndromes, such as optic neuropathy or transverse myelopathy, may cause diagnostic problems since they can be the first presentations in a number of demyelinating disorders including multiple sclerosis (MS) and collagen diseases
tumor necrosis factor (TNF) therapy and demyelinating event: A report indicates that adverse events such as the demyelinating lesion in the brain, optic neuritis, and neuropathy occurred after treatment with anti-TNF alpha therapy in collagen disease, and TNF antagonizing therapy showed worsening in a clinical trial with MS
Believing on the similarities of normal joints in humans and monkeys, we have employed a model of collagen-induced arthritis in Macaca fascicularis in an attempt to evaluate the histological alterations caused by such condition in the extracellular matrix of the articular cartilage

Summary

Introduction

Acute isolated neurological syndromes, such as optic neuropathy or transverse myelopathy, may cause diagnostic problems since they can be the first presentations in a number of demyelinating disorders including multiple sclerosis (MS) and collagen diseases. Acute Serum Amyloid A (A-SAA) is an acute phase protein strongly expressed in rheumatoid arthritis (RA) synovial tissue (ST) critically involved in regulating cell migration and angiogenesis These processes are dependent on downstream interactions between extracellular matrix and cytoskeletal components. Conclusions: These results indicate that Egr-1 contributes to IL-1mediated down-regulation of PPARg expression in OA chondrocytes and suggest that this pathway could be a potential target for pharmacologic intervention in the treatment of OA and possibly other arthritic diseases. Immune cell-derived microparticles (MPs) are present at increased amounts in synovial fluid of rheumatoid arthritis (RA) patients [1] and can activate disease-relevant signalling pathways in RA synovial fibroblasts (SF) [2,3].

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