Objective-To define the pattern of mRNA expression of all human matrix metalloproteinases (MMPs) described to date in rheumatoid arthritis (RA) and traumatic synovial membrane, in order to diVerentiate between a physiological tissue remodelling pattern and that associated with inflammatory tissue destruction. Methods-Analysis

The generation of wear debris is an inevitable result of normal usage of joint replacements. Wear debris particles stimulate local and systemic biological reactions resulting in chronic inflammation, periprosthetic bone destruction, and eventually, implant loosening and revision surgery. The latter may be indicated in up to 15% patients in the decade following the arthroplasty using conventional polyethylene. Macrophages play multiple roles in both inflammation and in maintaining tissue homeostasis. As sentinels of the innate immune system, they are central to the initiation of this inflammatory cascade, characterized by the release of pro-inflammatory and proosteoclastic factors. Similar to the response to pathogens, wear particles elicit a macrophage response, based on the unique properties of the cells belonging to this lineage, including sensing, chemotaxis, phagocytosis, and adaptive stimulation. The biological processes involved are complex, redundant, both local and systemic, and highly adaptive. Cells of the monocyte/ macrophage lineage are implicated in this phenomenon, ultimately resulting in differentiation and activation of bone resorbing osteoclasts. Simultaneously, other distinct macrophage populations inhibit inflammation and protect the bone-implant interface from osteolysis. Here, the current knowledge about the physiology of monocyte/macrophage lineage cells is reviewed. In addition, the pattern and consequences of their interaction with wear debris and the recent developments in this field are presented.

Objective. To measure cartilage pH in patients with osteoarthritis (OA) and to analyze the presence of cathepsin K, the recently discovered acidic endoproteinase, in phenotypically altered chondrocytes.Methods. Intraoperative measurements of the pH of clinically normal, fibrillated, superficially fissured, and deeply fissured cartilage surfaces (grades 0-3, respectively) in OA patients undergoing primary hip replacement surgery were performed with the use of a sting electrode sterilized with microbicidic plasma. Fluorescent pH probes were used for in situ assessment of cartilage matrix pH. Cathepsin K was assessed using quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry methods.Results. The pH of grade 0 cartilage surfaces was 7.1 ؎ 0.4 (mean ؎ SD), compared with 6.2 ؎ 0.9 (P < 0.05), 5.7 ؎ 1.0 (P < 0.001), and 5.5 ؎ 1.0 (P < 0.001) for grades 1-3 cartilage surfaces, respectively. Fluorescent pH probes and acid-dependent autocatalytic conversion of cathepsin K into its active, low molecular weight form in cartilage confirmed these findings. Cathepsin K messenger RNA levels increased in relation to the severity of OA, and the number of cathepsin K-containing chondrocytes increased from a mean ؎ SD of 12 ؎ 3 in grade 0 cartilage surfaces to 47 ؎ 7, 50 ؎ 6, and 100 ؎ 12 in grades 1-3 cartilage surfaces, respectively (P < 0.001 for all comparisons).Conclusion. Acid-activated, but pharmacologically inhibitable, cathepsin K is induced in phenotypically altered chondrocytes in OA. The findings suggest that cathepsin K, rather than neutral matrix metalloproteinases, degrades the superficial gliding surfaces of the articular hyaline cartilage in OA.Osteoarthritis (OA) is a common and crippling degenerative joint disease that affects the elderly population. In adult cartilage, chondrocytes occupy Ͻ5% of the total tissue volume. They reside in an avascular, anoxic environment and depend on anaerobic metabolism. Articular hyaline cartilage consists of a hydrated, proteoglycan-rich matrix in which a network of type II collagen-rich fibers is embedded (1,2). The hydrated proteoglycan matrix has a high swelling pressure, which is counteracted by the stiff collagen network (2). This gives unique biomechanical properties to the articular hyaline cartilage.While depletion of proteoglycans alone is considered to be reversible, once the collagen network is destroyed, the damage is permanent, because the articular hyaline cartilage has an almost nonexistent capacity to regenerate (3-5). Therefore, degradation of type II collagen is the crucial event in the pathogenesis of OA.OA has been considered to be strictly a wearand-tear disease, in which the destruction of the collagen fiber network is mechanically induced. However, it is now widely accepted that OA is a biochemically mediSupported by clinical EVO research grants (TYH 0056, TYH 0215, TYH 0341, and TYH 8307), an Invalid Foundation 9750/2 grant, and by the Academy of Finland/Centre for Technological Advancement (TEKES)/Ministry of Education (...