Boris Schminke

The Pathology of Bone Tissue during Peri-Implantitis

Dental implants are one of the most frequently used treatment options for tooth replacement. Approximately 30% of patients with dental implants develop peri-implantitis, which is an oral inflammatory disease that leads to loss of the supporting tissues, predominately the bone. For the development of future therapeutic strategies, it is essential to understand the molecular pathophysiology of human dental peri-implant infections. Here, we describe the gene and protein expression patterns of peri-implantitis bone tissue compared with healthy peri-implant bone tissue. Furthermore, cells from the osteoblastic lineage derived from peri-implantitis samples were immortalized and characterized. We applied microarray, quantitative reverse transcription polymerase chain reaction, fluorescence-activated cell sorting, and Western blot analyses. The levels of typical bone matrix molecules, including SPP1, BGLAP, and COL9A1, in patients with peri-implantitis were reduced, while the inflammation marker interleukin 8 (IL8) was highly expressed. RUNX2, one of the transcription factors of mature osteoblasts, was also decreased in peri-implantitis. Finally, the human telomerase reverse transcriptase immortalized cell line from peri-implantitis exhibited a more fibro-osteoblastic character than did the healthy control.

Human Migratory Meniscus Progenitor Cells Are Controlled via the TGF-β Pathway

Summary Degeneration of the knee joint during osteoarthritis often begins with meniscal lesions. Meniscectomy, previously performed extensively after meniscal injury, is now obsolete because of the inevitable osteoarthritis that occurs following this procedure. Clinically, meniscus self-renewal is well documented as long as the outer, vascularized meniscal ring remains intact. In contrast, regeneration of the inner, avascular meniscus does not occur. Here, we show that cartilage tissue harvested from the avascular inner human meniscus during the late stages of osteoarthritis harbors a unique progenitor cell population. These meniscus progenitor cells (MPCs) are clonogenic and multipotent and exhibit migratory activity. We also determined that MPCs are likely to be controlled by canonical transforming growth factor β (TGF-β) signaling that leads to an increase in SOX9 and a decrease in RUNX2, thereby enhancing the chondrogenic potential of MPC. Therefore, our work is relevant for the development of novel cell biological, regenerative therapies for meniscus repair.

Cartilage Repair In Vivo: The Role of Migratory Progenitor Cells

The most common diseases of the joints and its tissues are osteoarthritis and rheumatoid arthritis, with osteoarthritis being anticipated to be the fourth leading cause of disability by the year 2020. To date, no truly causal therapies are available, and this has promoted tissue engineering attempts mainly involving mesenchymal stem cells. The goal of all tissue repairs would be to restore a fully functional tissue, here a hyaline articular cartilage. The hyaline cartilage is the most affected in osteoarthritis, where altered cell–matrix interactions gradually destroy tissue integrity. In rheumatoid arthritis, the inflammatory aspect is more important, and the cartilage tissue is destroyed by the invasion of tumor-like pannus tissue arising from the inflamed synovia. Furthermore, the fibrocartilage of the meniscus is clearly involved in the initiation of osteoarthritis, especially after trauma. Recent investigations have highlighted the role of migratory progenitor cells found in diseased tissues in situ. In osteoarthritis and rheumatoid arthritis, these chondrogenic progenitor cells are involved in regeneration efforts that are largely unsuccessful in diseased cartilage tissue. However, these progenitor cells are interesting targets for a cell-based regenerative therapy for joint diseases.

Interleukin 17 inhibits progenitor cells in rheumatoid arthritis cartilage.

Mesenchymal stem cells are known to exert immunomodulatory effects in inflammatory diseases. Immuneregulatory cells lead to progressive joint destruction in rheumatoid arthritis (RA). Proinflammatory cytokines, such as tumour necrosis factor α (TNF‐α) and interleukins (ILs) are the main players. Here, we studied progenitor cells from RA cartilage (RA‐CPCs) that are positive for IL‐17 receptors to determinate the effects of inflammation on their chondrogenic potenial. IL‐17A/F reduced the chondrogenic potential of these cells via the upregulation of RUNX2 protein and enhanced IL‐6 protein and MMP3 mRNA levels. Blocking antibodies against IL‐17 positively influenced their repair potential. Furthermore, treating the RA‐CPCs with the anti‐human IL‐17 antibody secukinumab or the anti‐TNF‐α antibody adalimumab reduced the proinflammatory IL‐6 protein level and positively influenced the secretion of anti‐inflammatory IL‐10 protein. Additionally, adalimumab and secukinumab in particular reduced RUNX2 protein to promote chondrogenesis. The amelioration of inflammation, particularly via IL‐17 antagonism, might be a new therapeutic approach for enhancing intrinsic cartilage repair mechanisms in RA patients.

Antimicrobial effect and biocompatibility of novel metallic nanocrystalline implant coatings

AIM The present in vitro study was designed to evaluate the surface characteristics, biocompatibilities and antimicrobial effects of experimental titanium implant surfaces, coated by nanocrystalline silver, copper, and bismuth. Biocompatible and antimicrobial implant modifications could result in reduced biofilm formation on implant surfaces and therefore in less periimplant inflammation. FINDINGS Titanium discs (thickness 1 mm and 12 mm in diameter) were coated by pulsed magnetron-sputtering of nanocrystalline metals (bismuth, copper, and silver). Bismuth coatings revealed higher surface roughness values in comparison to silver and copper coatings via atomic force microscopy. Ion release after 168 h in culture medium was analyzed by inductively coupled plasma-mass spectrometry and showed significant different amounts of released copper (>120 000 µg/L), silver (550 µg/L) or bismuth (80 µg/L). No cytotoxic effect on HaCaT cell proliferation was detected on the uncoated Ti/TiO2 reference surfaces, the bismuth coatings and silver coatings. In contrast, copper-coated discs showed a strong cytotoxic effect. All three coatings exhibited antimicrobial effects by trend in the fluorometric Resazurin testing and significant localized antibacterial effects in live/dead microscopy after incubation of the specimens for 150 min in bacterial solution of S. epidermidis. CONCLUSIONS The tested metallic implant coatings (silver and bismuth) allowed surface modifications that may improve therapeutic approaches to biofilm prevention on dental implants.

Laminins and Nidogens in the Pericellular Matrix of Chondrocytes Their Role in Osteoarthritis and Chondrogenic Differentiation

The aim of this study was to investigate the role of laminins and nidogen-2 in osteoarthritis (OA) and their potential to support chondrogenic differentiation. We applied immunohistochemistry, electron microscopy, siRNA, quantitative RT-PCR, Western blot, and proteome analysis for the investigation of cartilage tissue and isolated chondrocytes in three-dimensional culture obtained from patients with late-stage knee OA and nidogen-2 knockout mice. We demonstrate that subunits of laminins appear in OA cartilage and that nidogen-2-null mice exhibit typical osteoarthritic features. Chondrogenic progenitor cells (CPCs) produced high levels of laminin-α1, laminin-α5, and nidogen-2 in their pericellular matrix, and laminin-α1 enhanced collagen type II and reduced collagen type I expression by cultured CPCs. Nidogen-2 increased SOX9 gene expression. Knockdown of nidogen-2 reduced SOX9 expression, whereas it up-regulated RUNX2 expression. This study reveals that the influence of the pericellular matrix on CPCs is important for the expression of the major regulator transcription factors, SOX9 and RUNX2. Our novel findings that laminins and nidogen-2 drive CPCs toward chondrogenesis may help in the elucidation of new treatment strategies for cartilage tissue regeneration.

Current concepts in stem cell therapy for articular cartilage repair.

Introduction: Hyaline articular cartilage is the connective tissue responsible for frictionless joint movement. Its degeneration ultimately results in complete loss of joint function in the late stages of osteoarthritis. Intrinsic repair is compromised, and cartilage tissue regeneration is difficult. However, new options are available to repair cartilage tissue by applying ESCs, MSCs and CPCs. Areas covered: In this review, the authors shed light on the different concepts currently under investigation for cartilage repair. Expert opinion: So far, there is no way to derive a chondrogenic lineage from stem cells that forms functional hyaline cartilage tissue in vivo. One alternative might be to enhance the chondrogenic potential of repair cells, which are already present in diseased cartilage tissue. CPCs found in diseased cartilage tissue in situ are biologically driven toward the osteochondrogenic lineage and can be directed toward chondrogenesis at least in vitro.

Fibulins and matrilins are novel structural components of the periodontium in the mouse

Periodontitis refers to inflammatory disease of the periodontal structures (the gingiva, dental cementum, periodontal ligament (PDL) and alveolar bone) that ultimately leads to their destruction. Whereas collagens are well-examined main components of the periodontium, little is known about the other structural proteins that make up this tissue. The aim of this study was to identify new extracellular matrix (ECM) components, including fibulins and matrilins, in the periodontium of mice. After sacrificing 14 mice (Sv/129 strain), jaws were prepared. Each tissue sample contained a molar and its surrounding alveolar bone. Immunohistochemistry was carried out on paraffin-embedded sections. Our results show that mice exhibit fibulin-3, -4 and -5 and matrilin-1, -2, -3 and -4 in PDL and in blood vessels of alveolar bone and PDL as well as in the pericellular matrix of osteocytes and cementocytes. In dental cementum, only fibulin-4 is expressed. For the first time, we show that fibulin-3, -4 and -5 and matrilin-1, -2, -3 and -4 are essential components of the periodontal tissues. Our findings indicate an association of these proteins with collagens and oxytalan fibers that might be of future interest in regenerative periodontitis therapy.