Άπόπτωσις

Modern hybrid daylilies have been described as the perfect perennial garden plant. Derived from about 30 wild species from the eastern parts of Asia, they are widely grown in North America, thanks in large part to the visionary hybridization program carried out by Dr Arlow Stout at the New York Botanical Garden in the first half of the 20th century. Owing to their diverse genetic background, there are varieties suitable for cultivation in gardens ranging from Florida to the southern portions of Canada. Daylilies have a number of merits that appeal to both the casual hobbyist and the fanatic collector. They are available in a dizzying array of shapes and patterns, and in almost every color except for true blue. Flower size and plant height range from the Lilliputian to the gargantuan, allowing them to fulfill nearly any landscaping need. They are able to survive almost total neglect from their owners—I am personally an expert on this point. The plants are prone to few diseases or pests, can tolerate a surprisingly long drought, and grow so densely that they are able to crowd out most common weeds. If that’s not enough, most parts of the daylily are edible and have even been used in traditional herbal medicine. In fact, daylilies have only one major shortcoming, a deficiency so characteristic that it inspired the great Linnaeus himself to christen their genus Hemerocallis, a word derived from Greek and usually translated as ‘‘beauty for a day. ’’ Daylily flowers open around sunrise, grow larger and more magnificent into the afternoon, only to fade and shrivel by sunset. By the next morning, a foul slime oozes from their rapidly decaying corpses, while a new crop of flowers greets the rising sun, blissfully oblivious to the grim fate that lurks, inevitably, only hours away. Although some cultivars may open somewhat earlier or survive a bit longer than others, this life cycle is embedded so deeply in the genetics of Hemerocallis that no human hybridizer has yet been able to alter it substantially. In 1972, three researchers from the University of Aberdeen proposed another botanical term derived from Greek to describe a similar process of ‘‘controlled deletion’’ that they and others had observed in human cells. They credited one of their colleagues from the university’s Greek department, Professor James Cormack, for suggesting the term ápóptvsi§ (apoptosis), a word that describes ‘‘the ‘dropping off’ or ‘falling off’ of petals from flowers, or leaves from trees. ’’ In contrast to the process of cell death known as coagulative necrosis, which they described as ‘‘invariably caused by noxious stimuli,’’ they noted that apoptosis played ‘‘an important role in the regulation of cell numbers under both physiological and pathological conditions. ’’ These conditions include undesirable processes such as teratogenesis and tissue atrophy, as well as normal embryonic development, where apoptosis facilitates the appearance of digital clefts and the involution of phylogenetic vestiges, and the homeostasis of adult tissues, where it serves to counterbalance mitotic cell reproduction. These authors observed that the process of apoptosis often appeared to be encoded in the cells themselves: ‘‘It seems clear . that in certain circumstances apoptosis is an inherently programmed event, determined by intrinsic ‘clocks’ specific for the cell type involved. ’’ Of interest to orthopaedic sports medicine specialists, apoptosis has been implicated in the pathogenesis of tendinopathy, including rotator cuff disease. In 2002, Yuan et al reported their analysis of biopsies from the edges of 25 torn rotator cuff tendons. Not only did the tissue show signs of mucoid degeneration, but the number of apoptotic cells was substantially elevated in comparison with control biopsy specimens taken from younger patients undergoing shoulder stabilization surgery. A subsequent study found up-regulation of apoptotic genes and proinflammatory cytokines in both torn supraspinatus tendons and macroscopically normal subscapularis tendons from the same patients. The finding of cytokines is noteworthy, since they have been used experimentally to create a model of mild tendinopathy in laboratory animals. In the current issue of the American Journal of Sports Medicine, Lee et al analyzed biopsy specimens from 3 different sites in torn rotator cuffs in 14 patients. Instead of harvesting their control specimens from much younger instability patients, they chose individuals of a similar age undergoing fixation of fractures of the proximal humerus. The samples that they obtained from the torn edge of the cuff, the posterior corner of the tear, or 1 cm medial to the tear margin, all showed increased numbers of apoptotic cells, as detected by TUNEL staining, in comparison with the control tissue. They also measured increased activity of cytochrome c and caspase 3/7, 8, and 9 at all 3 sites, implicating 2 different mechanisms of apoptosis. The authors concluded that torn rotator cuff tendons are affected by an apoptotic process that extends well beyond the actual tear site, a process that is not present in the supraspinatus tendons of similarly aged individuals who do not develop tears. These findings are consistent with the earlier study of Longo et al, which documented an abnormal histological appearance in samples taken a distance from the torn edge of rotator cuff tendons. Evidence of abnormal biology beyond the frayed margin of a torn rotator cuff suggests that optimizing the mechanical refixation of the torn The American Journal of Sports Medicine, Vol. 41, No. 10 DOI: 10.1177/0363546513506364 2013 American Orthopaedic Society for Sports Medicine