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Osteoarthritis (OA) is a group of common, chronic, and painful inflammatory joint diseases. One important finding in OA patients is a remarkable decrease in the molecular weight of hyaluronic acid (HA) in the synovial fluid of affected joints. Therapeutic HA is available to patients in most parts of the world as a viscosupplementation product for the treatment of OA. Previous clinical reports show that high molecular weight HA (HMWHA) more effectively relieves pain than low molecular weight HA (LMWHA). However, the mechanism behind this finding remains unclear. In this study, we investigated whether a LMWHA (Low-0.9 MDa) and two types of HMWHA (High-1.9 MDa and 6 MDa) differentially affected chondroregulatory action. We tested this using ATDC5 cell, a murine chondrocytic cell line widely used in culture systems to study chondrogenic differentiation. We found that HMWHA, especially hylan G-F 20 (High-6 MDa), significantly induced aggrecan and proteoglycan accumulation, nodule formation, and mRNA expression of chondrogenic differentiation markers in a time- and dose-dependent manner. In addition, we showed that HMWHA prevented TNF-α induced inhibition of chondrogenic differentiation, with no effect on cell proliferation or viability. These results reveal that HMWHA significantly promotes chondrogenic differentiation of ATDC5 cells in vitro, and suggest that HMWHA plays a significant chondroregulatory role in vivo. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:1619–1627, 2014.

This study was undertaken to investigate the age-related differences of monocyte chemotactic protein-1 (MCP-1) and matrix metalloproteinase-3 (MMP-3) expression in mouse intervertebral disc (IVD) and to determine whether MMP-3 plays a role in disc degeneration. Expression of MCP-1 and MMP-3 mRNA in mouse IVD was assessed by quantitative PCR. The ability of MCP-1 and MMP-3 expression in IVD to respond to TNF-α or TWEAK stimulation was examined by quantitative PCR, WB, ELISA, and immunohistochemistry. IVD derived from MMP-3-deficient and wild-type mice were compared using Safranin-O staining and immunohistochemistry. mRNA levels of MCP-1 and MMP-3 in IVD significantly diminished and the ability of MCP-1 or MMP-3 expression to respond to TNF-α or TWEAK stimulation was significantly reduced as age increased. IVD derived from 64-week-old wild-type mice showed clearly diffuse proteoglycan loss by Safranin-O staining and immunohistochemistry compared with younger mice. However, no loss of proteoglycan and typeII collagen were observed in IVD derived from 64-week-old MMP-3-deficient mice. MCP-1 and MMP-3 expression in mouse IVD showed age-related decreases. The response to inflammation in IVD also displayed age-related changes. Therefore, disc degeneration may vary with the patients' age and targeting MMP-3 may be a possible future therapeutic strategy for disc degeneration.

Background and Objectives The aim of this study is to clarify the extent of lymphatic spread of cancer cells using a novel genetic test to examine patients with thoracic esophageal squamous cell carcinoma (ESCC). Methods A total of 35 patients who underwent an esophagectomy with three-field lymph node (LN) dissection were eligible. The regional LN stations were categorized into the cervical (C), recurrent nerve (RN), paraesophageal (PE), tracheo-bronchial (TB), and perigastric (PG) nodes. Lymphatic spread was pathologically diagnosed with Hematoxylin-Eosin (HE) and anti-cytokeratin immunohistochemistry (IHC) staining, and CEA-mRNA expression was examined using the transcription-reverse transcription concerted (TRC) reaction. Results The rates of lymphatic spread with HE, IHC, and TRC were 7.2%, 10.1%, and 55.5%, respectively. The number of CEA-mRNA(+) LN stations significantly correlated with tumor depth, LN metastasis diagnosed by HE, and vascular invasions. CEA-mRNA expression was observed in 42.9%, 94.3%, 77.1%, 80.0%, and 82.9% of C, RN, TB, PE, and PG nodes, respectively. Conclusions The high frequency of CEA-mRNA expression suggests that systemic therapy is necessary in addition to esophagectomy with adequate LN dissection. Conversely, a relatively low frequency of CEA-mRNA expression in the C node does not support the routine dissection of the LNs in this area. J. Surg. Oncol. 2010;102:509–515. © 2010 Wiley-Liss, Inc.