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Heparin and histamine are not only important for causing immune response, but these inflammatory mediators are the key components of allergic reactions. Unlike basophils and eosinophils, neutrophils are considered both granulocytes and phagocytes. This type of immune cell internalizes bacterial pathogens, which become exposed to the toxic reactive oxygen species-filled granules in the cytoplasm of neutrophils. Another phagocytic cell is known as a macrophage. 83 Motile macrophages phagocytose bacterial patho© 2013 American Academy of Orthopaedic Surgeons Chapter 1: Molecular and Cell Biology in Orthopaedics Table 1 Commonly Used DMARDs for the Treatment of Rheumatoid Arthritis Drug Type Target Mechanism Abatacept Recombinant fusion protein Major histocompatibility complex receptors Adalimumab Recombinant monoclonal antibody TNF-α Anakinra Receptor antagonist IL-1 receptors Canakinumab Monoclonal IgG antibody IL-1β Etanercept Recombinant fusion protein TNF-α Infliximab Recombinant chimeric human-murine monoclonal antibody TNF-α Methotrexate Folate antagonist Dihydrofolate reductase Sulphasalazine Combination of sulphapyri- Unknown dine and 5-salicylic acid Humanized monoclonal IL-6 receptors antibody Binds to major hisotcompatibility complex receptors on antigenpresenting cells to block T cell activation Binds to TNF-α and inhibits the interactions of this cytokine to p55 and p75 receptors Binds to IL-1 receptors to block IL-1 proinflammatory signaling pathway Binds to IL-1β with high affinity to inhibit IL-1β and receptor association Competes with TNF-α receptor for the binding of TNF-α Binds to TNF-α.
24 These factors are critical to many important clinical disorders and have been implicated in pathologic bone resorption in metastatic and primary bone tumors, infection, prosthetic loosening, nonunion of fractures, osteoporosis, and periarticular bone loss in inflammatory arthropathies (Figure 12). 62 There are relatively few specific markers for the fibroblastic phenotype, and it appears in some ways that there is a default differentiation pathway of the production of fibroblasts from MSCs. Fibroblastic cells express fibronectin and can differentiate along some specialized pathways in generation of ligaments and tendons.
Bone remodeling provides an excellent prototypical example of matrix control of cell behavior and communication as well as integration of multiple signal inputs by cellmatrix interactions. 62 Osteoblasts provide the initial signals for bone resorption by osteoclasts, responding to stimuli such as PTH, with production of collagenase, which clears the area for osteoclast attachment as well as production of cytokines that stimulate osteoclast formation and activation. 79 The osteoclast releases and activates growth factors from the bone matrix as it resorbs the bone tissues that in turn stimulate nearby osteoblast progenitors to differentiate.