New thoughts on the pathophysiology of osteoarthritis: One more step toward new therapeutic targets

Abstract

Osteoarthritis is considered an illness in which a complex interaction between the tissues of the joint plays a significant role in the initiation and/or progression of this pathophysiology. We do not yet completely understand all the factors that are responsible for initiating the degradation and loss of the articular tissues. This paper summarizes the novelties of three such mechanisms. The first one points to some factors involved in the regulation of one growth factor family, the bone morphogenetic proteins, the second, the regulation of prostaglandin E(2) synthesis, and the third the factors involved in subchondral bone remodeling, all of which could be very significant events for osteoarthritis. This paper should help the reader better understand the most recent advances regarding the roles of these factors in this disease process, and how new therapeutic targets may be identified.

Strontium ranelate: The first agent of a new therapeutic class in osteoporosis

“…49 Moreover, the pathophysiology of hip or knee OA differs from that of spinal OA. 50 Previous studies have provided the preclinical basis for the in-vivo testing of strontium ranelate in OA. In human normal and OA chondrocytes that are treated with or without interleukin 1b (IL-1b), strontium ranelate has been shown to stimulate the synthesis of type II collagen and proteoglycan.…”

Inhibitory Effects of Pentosan Polysulfate Sodium on MAP-Kinase Pathway and NF-κB Nuclear Translocation in Canine Chondrocytes <i>In Vitro</i>

“…74(6): 707-711, 2012 In the treatment of canine osteoarthritis (OA), multiple therapeutic intervention tools are used for multimodal pain management, including systemic administration of nonsteroidal anti-inflammatory drugs (NSAIDs), intra-articular administration of hyaluronic acid, intravenous or intramuscular administration of disease-modyfying osteoarthritis drugs (DMOADs), the use of oral nutraceutical agents, rehabilitaion and weight management [20]. In particular, DMOADs are most likely to relief pain and other clinical symptoms directly related to joint pathologies [16].It is thought that the pathophysiology of OA is related with the imbalance of reparative and degradation processes leads to loose aggrecans and collagens from extracellular matrix (ECM) of hyaline cartilage, resulted in articular cartilage degeneration [1,15]. As catabolic enzymes of ECM, matrix metalloproteinase (MMP) and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) are playing major role in the process and in establishment of OA pathologies, to which DMOADs should target [19].…”

“…It is thought that the pathophysiology of OA is related with the imbalance of reparative and degradation processes leads to loose aggrecans and collagens from extracellular matrix (ECM) of hyaline cartilage, resulted in articular cartilage degeneration [1,15]. As catabolic enzymes of ECM, matrix metalloproteinase (MMP) and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) are playing major role in the process and in establishment of OA pathologies, to which DMOADs should target [19].…”

Phospholipases of Mineralization Competent Cells and Matrix Vesicles: Roles in Physiological and Pathological Mineralizations

“…PGE 2 mediates anti-inflammatory [230] as well as inflammatory effects [38,231,232]. Prostaglandins are potent multifunctional regulators in bone [233] having both stimulatory and inhibitory effects in bone metabolism [234,235]. Under physiological conditions, prostaglandins can stimulate bone formation by increasing proliferation and differentiation of osteoblasts [236].…”