The Machnism of Calcium Containing Cystals in Bone Remodeling

Project: A - Government Institutionb - Ministry of Science and Technology

Project Details

Description

Calcium containing arthritis is an inflammatory process which is accompanied by histopathologically characteristic bone destruction. This histological pattern suggests direct interactions between microcrystals and bone cells. The two most common types of calcium containing arthritis are calcium pyrophosphate dihydrate deposition disease (CPPD), and basic calcium phosphate (BCP) deposition disease. Bone remodeling involves the removal of mineralized bone by osteoclasts followed by the formation of bone matrix through the osteoblasts that subsequently become mineralized. The remodeling cycle consists of three consecutive phases: resorption, during which osteoclasts digest old bone; reversal, when mononuclear cells appear on the bone surface; and formation, when osteoblasts lay down new bone until the resorbed bone is completely replaced. Furthermore, through the RANK/receptor activator of NF-kappa B ligand (RANKL)/osteoprotegerin (OPG) system the processes of bone resorption and formation are tightly coupled allowing a wave of bone formation to follow each cycle of bone resorption, thus maintaining skeletal integrity. Bone destruction in calcium containing arthritis may occur because of a number of factors, including alterations in the function of osteoblast, osteoclasts, stromal cells, macrophages, and T cells. Osteoblasts are essential cellular components of the bone remodeling unit active through the expression of soluble factors and cell-to-cell interactions. They are also capable of phagocytosis of different solid particles as demonstrated by microscopy. Osteoblasts in direct contact with calcium containing crystals could play a role in the local bone destruction associated with chronic crystal-induced arthritis. Bone-resorbing osteoclasts can be matured in vitro by culture of monocyte/macrophage precursors in the presence of macrophage colony stimulating factor (M-CSF) and RANKL. These cells also express proteins that typify the osteoclast lineage, such as tartrate-resistant acid phosphatase (TRAP), cathepsin K, and the vitronectin receptor. Stromal cells also produce osteoprotegerin (OPG), a decoy receptor that prevents the binding of RANKL to its receptor RANK and thus inhibits osteoclastogenesis. The importance of osteoclasts in the pathogenesis of bone erosions in inflammatory arthritis, such as rheumatoid arthritis (RA) and psoriatic arthritis (PsA), has recently been emphasized. In these conditions, osteoclasts are present at sites of bone erosion, and osteoclasts formed from peripheral blood precursors exhibit increased resorptive activity. However, the mechanisms of bone destruction in calcium containing arthritis may differ from those in autoimmune inflammatory arthritis. We hypothesized that calcium containing crystals will influence the development and function of osteoblast and osteoclasts and cause bone destruction. The aim of the present study was to understand the molecular mechanisms of bone remodeling in calcium containing arthritis. Yet, it may be hoped that a better understanding of the pathogenesis of bone destruction could allow the development of new effective therapeutic strategies.
StatusFinished
Effective start/end date8/1/177/31/18

Keywords

  • Calcium containing arthritis
  • osteoblast
  • osteoclasts