What role does apoptosis play in other oral tissues?
Apoptosis seems to be necessary formaintaining homeostasis within continually renewing tissues such as the oral mucosa and skin (Funato et al.1999). Gingival tissue has a high cell turnover, and apoptosis has been demonstrated to occur in this tissue in 90% of the individuals tested (Yoshioka et al. 1996). Here, as in other parts of the body, apoptosis is essentially a counterbalance to mitosis. Unfortunately, the role of apoptosis in the differentiation of oral epithelial cells is not clear (Harada et al. 1998), and more work is required to fully describe the events associated with this process in normal oral tissues as a baseline to further study. What role does apoptosis play in bone?
In the process of bone remodelling, some osteoblasts die via apoptotic mechanisms, whilst those remaining become embedded as osteocytes (Ihbe et al. 1998, Jilka et al.1998). Many osteoclasts that lose their attachment to bone die by the process of apoptosis (Hughes & Boyce 1997). In this regard, a third term in addition to necrosis and apoptosis is oncosis, which describes cell death associated withs low is chaemia and cell swelling. This occurs to some osteoblasts during transition to osteocytes (Darzynkiewicz & Traganos1998).
TNF-a has been shown to enhance osteoblast apoptosis and may contribute to bone loss associated with inflammation (Hill et al. 1997, Jilka et al. 1998, Tsuboi et al. 1999). Neutrophils can also induce apoptosis of osteoblasts, demonstrating the relationship between inflammatory cells and bone resorption associated with inflammation (Kawakami et al.1997). On the other hand, growth factors, cytokines and other bone-stimulating hormones can reduce apoptosis of osteoblasts during periods of bone resorption (Hill etal.1997, Jilka et al.1998).
Apoptosis occurs in periradicular tissue during bone remodelling associated with orthodontic tooth movement (Rana et al. 2001). Certain mediators may limit the resorptive process and aid in bone formation during remodelling (Hill et al.1997).There is significant evidence that osteoblasts may be involved in the regulation of osteoclast apoptosis (Fuller et al. 1993; 1998, Green field et al.1999). In fact, most of the mediators that stimulate osteoclast activity seem to act through osteoblasts (Green field et al.1999). In general, however, factors that stimulate bone resorption inhibit osteoclast apoptosis and factors that inhibit bone resorption promote osteoclast apoptosis (Hughes & Boyce1997).
Apoptosis of osteoclast precursors may be one way that the osteoclast cell population is controlled (Hughes &Boyce1997), effectively reducing bone resorption (vanβt Hof & Ralston 1997). Furthermore, members of the TNF super-family inhibit osteoclast apoptosis (Fuller et al. 1998) and induce precursor maturation to mature functioning osteoclasts (Fuller et al.1998), thereby contributing to bone loss.
In the presence of high extracellular calcium concentrations as a result of ongoing resorptive processes, osteoclast apoptosis is induced (Lorget et al.2000). Similarly, oestrogen, glucocorticoids, bisphosphonates and TGF-b have been shown to stimulate apoptosis of osteoclasts (Green field et al.1999). What role does apoptosis play in immune cells?
Apoptosis is associated with the maintenance of immune cell homeostasis (Usherwood et al. 1999). Neutrophil production is balanced by apoptosis and clearance from tissues without inducing an inflammatory response (Onishi et al.1997). Apoptosis also plays a critical role in eliminating harmful or injured cells from tissues. This suggests its participation in inflammatory processes and in the resolution of inflammatory reactions (Onishi et al.1997). In periradicular lesions, apoptosis occurs predominantly in neutrophils (Takahashi et al.1999), a process that may be defective in abscess formation as a result of the acidic environment (Onishi et al. 1997). This lack of clearance of apoptotic cells can present a persistent antigen, inducing an autoimmune response (Onishi et al. 1997). Apoptosis of neutrophils is the major means of ending neutrophil-associated inflammation (Marshall & Watson 1997). Induction of this process therefore could be a way of minimizing inflammation that would occur as a result of neutrophil necrosis (Onishi et al. 1997), which is mediated and induced by certain environmental signals (Marshall & Watson 1997). There is also evidence that the failure of apoptotic mechanisms in neutrophils can contribute to pathogenesis of disease (Marshall &Watson1997). Neutrophils in exudate show delayed apoptosis and loss of TNF-a, which is necessary for neutrophil survival in the extravascular fluid (Seely et al. 1998). In addition, neutrophils in diabetics do not undergolipopolysaccharide (LPS)-induced inhibition of apoptosis. This may contribute to the increased susceptibility to infection observed in diabetic patients (Tennenberg et al. 1999). Calciumions have been shown to affect neutrophil apoptosis (Onishi et al.1997). The signalling mechanisms for other immune cells have been studied less extensively than those for neutrophils.