In this review we highlighted

two potential innate inflammatory mechanisms that may lead to development of synovitis in OA, the TLR pathway and the complement cascade (Fig. 3). Furthermore, we highlighted the roles of cytokines AC220 mouse and chemokines that play a role in the initiation and perpetuation of synovitis and OA symptoms. These pathways and mediators also may impact cartilage matrix homeostasis and peri-articular bone remodeling. In addition, the products associated with synovial inflammation may serve as surrogate markers of disease activity or responses to therapeutic interventions. Further understanding of mechanisms promoting synovial inflammation in OA may lead to identification of novel therapeutic targets for controlling symptoms and slowing structural progression in this disabling

joint disease. This study was supported by 1K08 AR057859-02, Mentored Clinical Scientist Career Development Award, from the National Institute of Arthritis, buy PTC124 Musculoskeletal and Skin Diseases (CRS). “
“Linear bone growth involves the replacement of a cartilaginous template by mineralized bone through endochondral ossification. This growth process is orchestrated by various actions at the growth plate, a developmental region consisting of chondrocytes in distinct cellular zones. The proliferation, hypertrophy and apoptosis of these growth plate chondrocytes are regulated by a tight array of factors ensuring effective cartilage JAK inhibitor mineralization and thus longitudinal growth [1]. Hydroxyapatite (HA) crystals form associated with the trilaminar membrane bound matrix vesicles (MV) which in the growth plate are localised to the mineralized longitudinal septae and form from the plasma membrane of the terminal hypertrophic chondrocytes [2]. Mineralization is a biphasic process which is under tight control so as to

ensure levels of calcium (Ca2 +) and inorganic phosphate (Pi) are permissive for effective HA formation [2]. Three molecules have been identified as imperative in controlling levels of the mineralization inhibitors inorganic pyrophosphate (PPi), and osteopontin [2] and [3]. These are alkaline phosphatase (ALP), a nucleotide pyrophosphatase/phosphodiesterase isozyme (NPP1), and the Ankylosis protein (ANK). However, mechanisms beyond the supply and hydrolysis of PPi likely exist to control chondrocyte matrix mineralization. Once such mechanism could involve matrix extracellular phosphoglycoprotein (MEPE, OF45). This was originally isolated and cloned from tumors of oncogenic hypophosphatemic osteomalacia (OHO) as a candidate substrate for phosphate-regulating gene with homologies to endopeptidases on the X chromosome (PHEX) [4]. MEPE is a 56–58 kDa SIBLING (small integrin-binding ligand N-linked glycosylated) protein along with dentin matrix protein 1 (DMP1), osteopontin (OPN), dentin sialophosphoprotein (DSPP) and bone sialoprotein (BSP) [5].