The Janus kinase (JAK) signal transducer and activator of transcription (STAT) signaling pathway serves as an important downstream mediator for a variety of cytokines, hormones, and growth factors. Emerging evidence suggests JAK/STAT signaling pathway plays an important role in bone development, metabolism, and healing. In this light, pro-inflammatory cytokines are now clearly implicated in these processes as they can perturb normal bone remodeling through their action on osteoclasts and osteoblasts at both intra- and extra-articular skeletal sites. Here, we summarize the role of JAK/STAT pathway on development, homeostasis, and regeneration based on skeletal phenotype of individual JAK and STAT gene knockout models and selective inhibition of components of the JAK/STAT signaling including influences of JAK inhibition in osteoclasts, osteoblasts, and osteocytes.

Ultrasound (US) and magnetic resonance imaging (MRI) are recommended in the diagnostic process of rheumatoid arthritis. Research on its comparability in early disease phases is scarce. Therefore, we compared synovitis and tenosynovitis detected by US and MRI on joint/tendon level. Eight hundred forty joints and 700 tendons of 70 consecutive patients, presenting with inflammatory arthritis or clinically suspect arthralgia, underwent US and MRI of MCP (2–5), wrist and MTP (1–5) joints at the same day. Greyscale (GS) and power Doppler (PD) synovitis were scored according to the modified Szkudlarek method (combining synovial effusion and hypertrophy) and the recently published EULAR-OMERACT method (synovial hypertrophy regardless of the presence of effusion) on static images. US-detected tenosynovitis was scored according to the OMERACT. MRI scans were scored according to the RAMRIS. Test characteristics were calculated on joint/tendon level with MRI as reference. Cut-off for US scores were ≥ 1 and ≥ 2 and for MRI ≥ 1. Compared to MRI, GS synovitis according to EULAR-OMERACT (cut-off ≥ 1) had a sensitivity ranging from 29 to 75% for the different joint locations; specificity ranged from 80 to 98%. For the modified Szkudlarek method, the sensitivity was 68–91% and specificity 52–71%. PD synovitis had a sensitivity of 30–54% and specificity 97–99% compared to MRI. The sensitivity to detect GS tenosynovitis was 50–78% and the specificity 80–94%. For PD tenosynovitis, the sensitivity was 19–58% and specificity 98–100%. Current data showed that US is less sensitive than MRI in the early detection of synovitis and tenosynovitis, but resulted in only few non-specific findings. The higher sensitivity of MRI is at the expense of less accessibility and higher costs.

Background In rheumatoid arthritis (RA), hand synovitis appears especially in wrist, metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints. In hand osteoarthritis (OA), potential inflammatory changes are mainly present in PIP and distal interphalangeal (DIP) joints. Joint inflammation can be visualised by fluorescence optical imaging (FOI) and musculoskeletal ultrasound (US). Objective Comparison of the amount and distribution of inflammatory signs in wrist and finger joints of the clinically dominant hand in patients with OA and RA by FOI and gray-scale (GSUS) and power Doppler US (PDUS). Methods FOI and GSUS/PDUS were performed in 1.170 joints (wrists, MCP, PIP, DIP) in 90 patients (67 RA, 23 OA). Joint inflammation was graded by a semiquantitative score (0–3) for each imaging method. Results GSUS/PDUS showed wrist and MCP joints mostly affected in RA. DIP joints were graded higher in OA. In FOI, RA and OA featured inflammatory changes in the respective joint groups depending on the phase of fluorescence dye flooding. Conclusions US and FOI detected inflammation in both RA and OA highlighting the inflammatory component in the course of OA. The different inflammatory patterns and various shapes of fluorescence enhancement in FOI may offer opportunities to distinguish and determine the inflammatory status in both diseases.

Mesenchymal stem/stromal cells (MSCs) are stem cells of the connective tissue, possess a plastic phenotype, and are able to differentiate into various tissues. Besides their role in tissue regeneration, MSCs perform additional functions as a modulator or inhibitor of immune responses. Due to their pleiotropic function, MSCs have also gained therapeutic importance for the treatment of autoimmune diseases and for improving fracture healing and cartilage regeneration. However, the therapeutic/immunomodulatory mode of action of MSCs is largely unknown. Here, we describe that MSCs express the inhibitory receptor CTLA-4 (cytotoxic T lymphocyte antigen 4). We show that depending on the environmental conditions, MSCs express different isoforms of CTLA-4 with the secreted isoform (sCTLA-4) being the most abundant under hypoxic conditions. Furthermore, we demonstrate that the immunosuppressive function of MSCs is mediated mainly by the secretion of CTLA-4. These findings open new ways for treatment when tissue regeneration/fracture healing is difficult.

Ziel: Untersuchung der Hand- und Fingergelenke von Patienten mit rheumatoider Arthritis (RA) mittels B-Bild-, Power-Doppler- und kontrastmittelgestütztem Ultraschall (US) und Vergleich dieser Befunde mit MRT-, klinischen (DAS28) und Labordaten (BSG; CRP). Material und Methoden: Die US-Verfahren wurden vor Therapieumstellung (t0) sowie nach 3, 6 und 12 Monaten (t12) angewendet; MRT-Bilder zum t0- und t12-Zeitpunkt erhoben und dessen Ergebnisse als Referenzstandard betrachtet. Mittels kontrastmittelgestütztem US ist die klinisch am stärksten betroffene Gelenkregion untersucht worden. Synovialitis-Summenscores wurden mittels B-Bild- und Power-Doppler-US gebildet. Ergebnisse: Der kontrastmittelgestützte US wurde mittels dreier Methoden angewendet: Kontrastanreicherung, Slope und semiquantitativ (0 – 3), welche untereinander, zum B-Bild-Ultraschall, zum CRP als auch zur MRT mit den höchsten Korrelationskoeffizienten (r = 0,56, r = 0,55, r = 0,57; jeweils p < 0,05) signifikant korrelierten. Die per B-Bild erhobenen Summenscores konnten zeigen, dass die palmare Fingergelenksregion signifikant häufiger von Synovialitis betroffen war als die dorsale Seite (p = 0,001). Die untersuchten Handgelenksregionen waren im Power-Doppler-Ultraschall häufiger von dorsal entzündlich verändert (p = 0,0004). Im Verlauf korrelierten die Ergebnisse des B-Bild- und Power-Doppler-Ultraschalls signifikant. Schlussfolgerung: B-Bild-, Power-Doppler- und kontrastmittelgestützter US sind gute Methoden zur Aufdeckung und Verlaufsuntersuchung von Synovialitis an den Hand- und Fingergelenken von Patienten mit RA, von denen der kontrastmittelgestützte US, im Vergleich zur MRT, am sensitivsten war. Die bildgebenden Methoden spiegelten die Antwort auf eine TNFα-Inhibitor-Therapie adäquat wider. Purpose: To evaluate wrist and finger joints in patients with rheumatoid arthritis (RA) by grayscale, power Doppler (PD) and contrast-enhanced musculoskeletal ultrasonography (US) and to compare these findings with MRI, clinical (DAS28) and laboratory (ESR; CRP) data. Materials and Methods: US was performed at baseline (t0) and after three, six and twelve (t12) months before and after a change of medical treatment. MRI was carried out at t0 and t12 and used as the reference method. Contrast-enhanced US was used to assess one clinically most affected joint region. Different semiquantitative synovitis scores were calculated by grayscale and PD US. Results: Contrast-enhanced US results evaluated by enhancement, slope and semi-quantitative assessment significantly correlated to each other, to grayscale US, CRP, as well as to MRI with the highest correlation coefficients for the used contrast-enhanced US modes (r = 0.56, r = 0.55, r = 0.57; each p < 0.05). Sum scores evaluated by grayscale US showed that synovial inflammation in finger joints was detected significantly more frequently in the palmar aspect than on the dorsal side (p = 0.001). Using power Doppler US, the wrists were significantly more inflamed from dorsal than on the palmar side (p = 0.0004). Significant longitudinal correlations between grayscale and power Doppler US scores were detected. Conclusion: Grayscale, power Doppler and contrast-enhanced US are accurate tools for the detection and follow-up of synovitis in RA wrist and finger joints, with contrast-enhanced US being most sensitive compared to MRI. All imaging methods reflected a good response to TNFα blocking therapy.