Recovery of function in osteoarthritic chondrocytes induced by p16INK4a-specific siRNA in vitro.

OBJECTIVE: To demonstrate the roles of p16(INK4a) in the senescence of human chondrocytes and the progression of osteoarthritis (OA). METHODS: Immunohistochemistry and reverse transcriptase polymerase chain reaction (RT-PCR) were performed to examine p16(INK4a) expression in fetal, normal age-matched and OA cartilage, and Western blot was used in primary cultured chondrocytes from different origins. To explore a functional p16(INK4a) knockdown in OA chondrocytes, the primary cultured cells were treated with p16(INK4a)-specific small interfering ribonucleic acids (siRNAs). Expression of p16(INK4a), p14(ARF) and p53 was observed by Western blot and RT-PCR. The phosphorylation status of pRb, senescence-associated beta-galactosidase (SA-beta-gal), cell G1/S transition and cell proliferation were studied by Western blot, histological staining, 3H-thymidine incorporation and cell counts respectively. Expression of the collagen I, collagen II and aggrecan genes was measured by semiquantitative RT-PCR. To establish the response of chondrocytes to cytokines, cells were treated with transforming growth factor-beta1 (TGF-beta1) or interleukin-1alpha (IL-1alpha) and examined for incorporation of 3H-thymidine, 3H-proline and 35S-sulphate respectively. RESULTS: A significant increase of p16(INK4a) was detected in OA chondrocytes compared with normal age-matched and fetal chondrocytes (P<0.01) in vivo and in vitro. Treated with p16(INK4a)-specific siRNAs, OA chondrocytes displayed a significant decrease in p16(INK4a) expression with an increase of phosphorylated pRb, but no alteration of p14(ARF) and p53 expression, followed by decreases of senescent features and increases in the expression of some chondrocyte-specific genes and overall repair capacity. CONCLUSIONS: p16(INK4a) is instrumental in the senescence of human articular chondrocytes or OA. The reduction of p16(INK4a) by RNA interference (RNAi) contributed to the recovery of osteoarthritic chondrocytes, suggesting that p16(INK4a) may be a viable future therapeutic candidate.

The mechanical-chemical attachment between the artificial articular cartilage (PVA-hydrogel) and metal substrate (or underlying bone).

PVA-hydrogel has excellent biocompatibility as well as preferable tribological characteristics as an artificial articular cartilage. One of the most difficult problems is the attachment of PVA-hydrogel to the underlying bone (or metal substrate). In the present study, the micro-mechanical attachment between the PVA-hydrogel and metal fibre mesh was at first accomplished to obtain a composite artificial cartilage device (CACD), then the surface of fibre mesh is chemically bonded to the metal substrate (or underlying bone) by adhesive (PMMA). This method can be used to accomplish mechanical-chemical attachment between composite artificial cartilage device and underlying bone (or metal substrate). Microstructure analysis and mechanical tests indicate that the CACD can be firmly bonded to the metal substrate (or underlying bone).

Pathogenetic effects of salted pork in an area of China with high-risk for stomach cancer.

AIM: To study the pathogenetic effects of salted pork (SP) (a special food in Zhuanghe City, a region of northern China that is a high-risk area for stomach cancer) on stomach cancer, and a provide scientific basis for the primary prevention of stomach cancer in this high-risk region. METHODS: This study consisted of three distinct parts. The first part involved a study of SP mutagenicity and employed both the Ames test and micronuclei assay using V79 cells. The second part included a study of SP's effect on the gastric mucosa of residents in the Zhuanghe area who had consumed SP for more than ten years. Additionally, these studies involved an analysis of the dose effect relationship between SP and pathological changes in gastric mucosa, with a total of 300 cases analyzed. The third part of this study involved an observation of the mucosal lesions from experimental dogs by both gastroscopy and mucosal biopsy. Six healthy male dogs were selected, three were fed with SP, and the others served as controls. RESULTS: This study revealed that SP extract could mutate Salmonella typhimurium TA98 and induce an increase in both the micro nuclei rate (MNR) and micro nuclei cell rate (MNCR) of V79 at a dose range of 20-80 µL/mL. There were significant dose-effect relations between SP and either MNR or MNCR. Pathological changes in the gastric mucosa of local residents who had consumed SP were significantly different from those of the control group. In people who had consumed SP for ten years, mucosal lesions were found that contained evidence of necrosis and erosion; In those who consumed SP for ten-20 years, both hyperplasia and dysplasia were seen in addition to the above lesions. In individuals who had consumed SP for 20-30 years, severe dysplasia and malignant changes were found. Furthermore, SP had damaging effect on the gastric mucosa of dogs that were fed SP. The mucosal lesions became more severe with increased feeding time. CONCLUSION: SP is a strong mutagen and long-term SP exposure may result in repeated gastric mucosal damage and repair, ultimately leading to severe dysplasia and malignancy.

[Clinical significance of congenital fusion of cervical vertebrae: a report of 87 cases].

Based on clinical analysis of 87 cases with congenital fusion of cervical vertebrae, the clinical significance of these lesions was discussed in detail. It was found that the C 2-3 and then the C 3-4 were the sites of frequent involvement. Fusion of 2 to 3 segments was common and showed no clinical signs of abnormality, nor associated with any other malformations. While fusion of multiple segments, though rare, was often associated with other anomalies such as short neck, lowered posterior hair line, webbed neck and malformation of internal organs and other bones. Single lesion does not give rise to symptoms until late when degenerative changes have taken place in the unfused vertebrae in most cases, or following trauma in occasional patients, usually of neurologic upsets. However, fusion at several especially levels, fusion of C 2-3 with occipitalization of atlas predisposes the nerve to damage. In short, remedy is only necessary for cases with symptoms: conservative treatment for those with symptoms caused by radiculopathy, and operation for those with symptoms of myelopathy.

Anterior intervertebral disc excision and bone grafting in cervical spondylotic myelopathy.

An analysis of 121 cases of cervical spondylotic myelopathy treated by anterior excision of the disc and fusion was undertaken. All patients were followed at least six months, and follow-up averaged 22 months. Results showed that 97.5% of patients had no aggravation of symptoms, 90.9% were improved, and 72.6% were able to resume normal activity. Surgical intervention can greatly improve the prospects of patients with severe cervical spondylotic myelopathy, and its use should not be lightly ruled out. Autografts yield higher fusion rates and better overall results than homografts. Selection of the number and level of discs to be excised depends upon clinical and roentgenographic indications, as well as the myelogram and the amount of fluid injected into the discs.