Apoptotic pathways in degenerative disk lesions in the wrist.
ABSTRACT Degenerative articular disk perforations of the triangular fibrocartilage (TFC) of the wrist could result from chronic loading of the ulnocarpal joint. Apoptosis played a crucial role in fibrocartilage cell loss, and the purpose of this study was to clarify which apoptotic pathway was involved in the development of degenerative disk lesions. We also investigated whether ulna length played an etiologic role in the occurrence of fibrocartilage cell loss.
Included in the study were 17 patients with degenerative articular disk tears of the TFC (Palmer type 2C). After arthroscopic debridement of the TFC, histologic sections were examined to assess the presence of apoptosis. Apoptosis was determined by use of caspase 3, caspase 8, and caspase 9 immunohistochemistry. Furthermore, Fas ligand and BID (BH3 interacting domain death) agonist were applied for immunohistochemical analysis.
Cells positive for caspase 3, caspase 8, caspase 9, Fas ligand, and BID were found in all specimens. The number of cells positive for caspase 3 and BID was significantly increased in specimens from patients with an ulna-positive variance. In contrast, for cells positive for caspase 8, caspase 9, and Fas ligand, no significant difference was found between specimens from patients with an ulna-positive variance and those from patients with an ulna-neutral/ulna-negative variance.
The extrinsic and intrinsic apoptotic pathways are involved in the development of degenerative disk lesions. Fibrocartilage cell loss occurs mainly through the intrinsic apoptotic pathway. The accumulation of apoptotic cells is not significantly different between the 3 zones of the TFC. It could be verified that ulna length is correlated with fibrocartilage cell loss.
Ulnar shortening is a valuable treatment option for degenerative TFC lesions. Knowledge of the specific apoptotic pathway that is causing degenerative disk lesions is critical in selecting the appropriate and most beneficial therapeutic treatment to halt further cell loss and the degeneration of the TFC.
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ABSTRACT: Traumatic and degenerative disc lesions cause ulnar-sided wrist pain. To date, anatomical investigations of cadaver triangular fibrocartilage discs examining the innervation of the triangular fibrocartilage complex have found no evidence of nerve fibers in the healthy disc. In this study, we immunohistologically investigated biopsies from patients with either central traumatic or degenerative disc lesions, to determine the existence of nerve fibers. We hypothesized that an ingrowth of nerve fibers causes ulnar-sided wrist pain associated with traumatic and degenerative disc lesions. We included 32 patients with a traumatic Palmer 1A lesion and 17 patients with a degenerative Palmer 2C lesion in the study. We obtained a biopsy of each patient and stained the specimen with protein gene product 9.5 for nerve fiber detection. There were no nerve fibers in either traumatic or degenerative disc lesions. In addition, the marginal areas of the biopsies showed no evidence of nerve fibers. Traumatic and degenerative disc lesions show no ingrowth of nerve fibers.The Journal of hand surgery 03/2011; 36(5):843-6. · 1.33 Impact Factor
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ABSTRACT: Little information exists on the contribution of apoptosis to pathological tendon changes in rotator cuff tendinopathy. The purpose of this study was to quantitate the rate of tenocyte apoptosis in torn supraspinatus tendons and in the matched intact subscapularis and to examine the potential relation between apoptotic index (AI) and tendon pathology. In addition, the authors examined tenocyte density, proliferation rate and p53 gene expression patterns to gain further insight into relevant pathological mechanisms in the torn suprapinatus. 15 torn supraspinatus tendons with matched intact subscapularis tendon samples and 10 reference subscapularis samples were collected. Immunohistochemistry was used to define the AI (F7-26), proliferation rate (Ki67) and presence of p53 (M7001). Tendon degeneration was evaluated according to the Bonar scale. Expression of p53 and relevant genes (n=84) was examined on a subset of samples using microfluidic arrays. The AI was significantly increased in torn supraspinatus tendon and matched subscapularis tendon (R² =0.5742; p=0.0005). Cell density and proliferation rate were also elevated in torn supraspinatus compared with reference subscapularis tendons (p<0.05). A significant increase in p53 occurred specifically in torn supraspinatus tendon (p<0.05), and several genes encoding p53-inhibiting proteins were downregulated in association, including HDAC1 (p<0.05), MDM4 (p<0.001) and PPM1D (p<0.05). Our results suggest that tenocyte apoptosis results from more than one mechanism in the injured rotator cuff, including both intrinsic factors related specifically to the torn supraspinatus tendon, as well as a more generalised effect on the adjacent subscapularis tendon.British journal of sports medicine 04/2011; 45(13):1035-9. · 3.67 Impact Factor
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ABSTRACT: PURPOSE: The role of apoptosis in the progression of rotator cuff tendinopathy remains poorly understood. In particular, the extent of apoptosis in the partially torn supraspinatus tendon has not been well examined. METHODS: Biopsies were obtained from nine partially torn supraspinatus tendons, from the matched intact subscapularis tendons, and from 10 reference subscapularis tendons. Immunohistochemistry was used to assess the density of apoptotic cells (activated caspase-3; Asp175), proliferation (Ki67), and p53 (M7001), a key protein involved in regulating cell death. The Bonar scale was used to evaluate tendon degeneration. RESULTS: The density of apoptotic tendon cells and the density of cells expressing p53 were significantly increased in both the partially torn supraspinatus tendons and in the matched subscapularis tendons, compared with uninjured reference tendons. The Bonar score revealed significant tendon degeneration in the partially torn supraspinatus tendons compared with both matched and reference subscapularis tendons. Tendon cell proliferation was significantly increased in the partially torn supraspinatus tendons compared with reference subscapularis tendons. CONCLUSIONS: Partial-thickness tears of the supraspinatus tendon demonstrated an increased density of apoptotic, p53+ tendon cells. The fact that apoptosis was accompanied by increased tendon cell proliferation suggests that apoptosis may be related to an ongoing injury-repair process. Increased tenocyte apoptosis may be a relatively early feature in rotator cuff tendinopathy and could represent a possible target for therapeutic intervention.Knee Surgery Sports Traumatology Arthroscopy 10/2012; · 2.68 Impact Factor