Smoking delays chondrogenesis in a mouse model of closed tibial fracture healing.

Smoking delays the healing process and increases morbidity associated with many common musculoskeletal disorders, including long bone fracture. In the current study, a murine model of tibial fracture healing was used to test the hypothesis that smoking delays chondrogenesis after fracture. Mice were divided into two groups, a nonsmoking control group and a group exposed to cigarette smoke for 1 month prior to surgical tibial fracture. Mice were euthanized at 7, 14, and 28 days after surgery. The outcomes measured were immunohistochemical staining for type II collagen protein expression as a marker of cartilage matrix and proliferating cell nuclear antigen (PCNA) staining to measure proliferation at the site of injury. Toluidine blue staining and histomorphometry were used to quantify areas of cartilaginous and noncartilaginous fracture callus. Radiographs were analyzed for evidence of remodeling after injury. At day 7 after injury, mice exposed to cigarette smoke had a smaller fracture callus with less cartilage matrix compared to controls. Proliferation was present at high levels in both groups at this time point, but proliferating cells had a more immature morphology in the smoking group. At day 14, chondrogenesis was more active in smokers compared to controls, while a higher percentage of bone was present in the control animals. At day 28, X-ray analysis revealed a larger fracture callus remaining in the smoking animals. Together, these findings show that the chondrogenic phase of tibial fracture healing is delayed by smoking. This study represents, to our knowledge, the first analysis of molecular and cellular mechanisms of healing in a smoking mouse fracture model.     

胶原酶在治疗烧、创伤创面中应用的临床观察

目的　探讨胶原酶制剂治疗烧、创伤创面的临床疗效。方法　创面常规清创后涂胶原酶制剂外敷凡士林纱布或无菌纱布包扎 ,每日或隔日换药。结果　本组 2 2 0例 ,其中 4 4例浅Ⅱ度烧伤创面用药后 8～ 11d基本愈合 ,83例深Ⅱ度创面 12～ 18d愈合 ,4 2例Ⅲ度创面用药 7～ 10d基本达到植皮条件 ,5 1例创伤所致肌腱、韧带、骨骼等外露创面用药 12～ 19d基本具备植皮条件。结论　胶原酶治疗烧、创伤创面 ,具有加速坏死组织液化、促进损伤部位残留表皮细胞生长、利于创面修复和减轻瘢痕的作用     

汉族、哈萨克族Graves病患者血清CoL IV、LN和HA测定分析

用放免法(单克隆抗体)测定汉、哈萨克族Graves病未经治疗患者66例及正常对照组55例血清中Ⅳ型胶原(CoLⅣ)、板层素(IN)和透明质酸(HA),结果Graves病患者血清CoLⅣ、LN浓度明显升高,HA浓度明显降低,与正常对照组相比均有显著性差异(分别P<0.001、P<0.05、P<0.05),汉族与哈萨克族患者之间、对照组之间相比均无显著性差异(P>0.05),它反映了Graves病患者体内基底膜合成和分解代谢紊乱。     

Collagen synthesis activities of chondrocytes from histologically distinct zones of chick embryo tibia

Monolayer cultures of 12-day chick embryo chondrocytes from the regions of dividing (zone 1), elongated (zone 2), and hypertrophied (zone 3) chondrocytes in the tibial cpiphyseal growth plate were analyzed for their capacity to synthesize types II, IX, X, and XI collagens. Synthesis of types II and IX collagens was markedly elevated in the zone 2 culture, while type X collagen synthesis was maximal in zone 3. Type XI collagen was synthesized at low rates in all cultures, with some elevation of its rate in zones 2 and 3. In terms of mol percent of total collagen synthesis, types II and IX collagens decreased from zone 1 to zone 3, while type X collagen increased progressively. Thus, the composition of the extracellular collagens produced by the different zones changed markedly during chondrocyte differentiation. In addition, type X collagen was released exclusively into the culture medium, whereas type XI collagen was retained in the extracellular cell-associated matrix. In contrast, types II and IX collagens were found in both the culture medium and the cell matrix pools. Although types II and IX collagens showed similar changes during differentiation, the synthetic molar ratios of these two collagens varied from 3 to 18 in different cultures, suggesting that the synthesis of these two products is not tightly coupled in these cells.     

粉防己碱和氯丙嗪对人胚肺成纤维细胞胶原和透明质酸合成的影响(英文)

目的：研究粉防己碱(Tet)和氯丙嗪(Chl)对人胚肺成纤维细胞胶原与透明质酸(HA)合成的影响,为应用钙拮抗剂防治器官纤维化提供依据.方法:采用[~3H]脯氨酸掺入和放射免疫法分别测定胶原与HA合成.结果:Tet 5—80 μmol L~(-1)和Chl 10—40 μmol L~(-1)均以浓度依赖方式抑制胶原与HA合成.Tet 5—20μmol L~(-1))对细胞无明显毒性却显著抑制胶原与HA合成(P<0.01).结论:Tet在低浓度(5—20μmol L~(-1))时对细胞无明显毒性作用而显著抑制成纤维细胞胶原与HA合成,可望成为治疗器官纤维化的有效药物.     

Specific Changes of Urinary Excretion of Cross-Linked N-Telopeptides of Type I Collagen in Pre- and Postmenopausal Women: Correlation with Other Markers of Bone Turnover

Urinary excretion of cross-linked N-telopeptide of type I collagen (NTx) has been reported to be a specific marker of bone resorption [18]. We assessed a new immunoassay for NTx as an indicator of changes in bone resorption caused by spontaneous menopause and compared cross-sectionally the levels of urinary NTx, hydroxylysylpyridinoline (HP), lysylpyridinoline (LP), hydroxyproline (OH-Pr), other serum biochemical indices, and lumbar spine and proximal femur bone mineral density (BMD). Eighty-one Japanese women aged 22–77 participated in this study; 36 were premenopausal and 45 were postmenopausal. Urinary HP, LP, and NTx stayed at low levels in the premenopausal period and rose 21%, 30%, and 67% in the postmenopausal period, respectively. The rise in LP and NTx was statistically significant (P < 0.01), suggesting that NTx is mostly released from bone matrix when bone resorption is accelerated. When premenopausal women were divided into two age groups and postmenopausal women were divided into two groups according to years since menopause (YSM) there were significant differences in LP and NTx between women <4 YSM and women aged <40 and those women aged 41+ (P < 0.01 and P < 0.05, respectively). A significant 110% increase in urinary NTx and a 48% increase in urinary LP were observed in postmenopausal women compared with age-matched premenopausal women aged 45–55. All biochemical markers other than serum PTH correlated significantly with each other (r = 0.243–0.858, P < 0.05–0.0001). Urinary NTx inversely correlated with lumbar spine BMD. When postmenopausal women were divided into three groups, the correlation between bone resorption and formation markers in women 0-1 YSM was greater than in women 2–10 YSM and in women 11 + YSM, indicating that resorption and formation are coupled at the early postmenopausal period. We conclude that urinary NTx is responsive to changes in bone metabolism caused by estrogen deficiency and may be a more sensitive and specific marker than HP, LP, or OH-Pr in the early postmenopausal years. Received: 15 February 1995 / Accepted: 18 October 1996     

Can bone metabolism markers be adopted as an alternative to scintigraphic imaging in monitoring bone metastases from breast cancer?

Bone scintigraphy plays a major role in the diagnosis of bone metastases. The clinical utility of new biochemical markers of bone metabolism has recently been investigated in various bone diseases. This study evaluated the role of some bone metabolism markers in comparison with bone scan in the follow-up of breast cancer patients. We studied 149 patients with breast cancer, 33 (22%) of whom had bone metastases. IRMAs were used for the evaluation of blood levels of osteocalcin, bone alkaline phosphatase (BAP), the C-terminal propeptide of type I procollagen and the C-terminal cross-linked telopeptide of type I collagen (ICTP). Multivariate regression analysis showed that menopausal status (P=0.007) and metastatic bone lesions (P=0.001) affected bone marker levels. When considering post-menopausal women, the only subset in which bone metabolism marker behaviour could be reliably investigated, we found a high degree of overlap in marker distribution for scan-positive and scan-negative patients. Discrimination between scan-negative and scan-positive patients based on the above markers, taken singly or jointly, was assessed by means of logistic discriminant analysis. The best discrimination was achieved with BAP, closely followed by ICTP. BAP and ICTP together gave a slight improvement over the use of the two markers separately. However, even in this case the degree of discrimination was poor and its clinical utility was limited. In fact, to achieve a specificity of 95%, the sensitivity of the test was about 20%; conversely, with a sensitivity of 95%, the specificity was below 10%. In conclusion, based on our findings, we believe that blood levels of the investigated markers cannot replace bone scintigraphy in the follow-up of breast cancer patients for the early detection of bone metastases. Received 14 April and in revised form 5 July 1997     

Acrometageria: A spectrum of “premature aging” syndromes

A child with manifestations of acrogeria and metageria, two “premature aging” syndromes, is presented. Because of his indistinct phenotype and because the question has been previously raised as to whether these conditions are separate, we propose the designation of acrometageria to describe this phenotypic continuum. As there is much in common clinically between acrometageria and the syndrome of type III procollagen deficiency (Ehlers-Danlos type IV), it might be presumed that a similar pathogenesis for acrometageria exists. This possibility has been tested previously, without demonstrating specific quantitative or qualitative deficits, but with some indirect evidence that collagen metabolism is deranged in these patients. One such crude indicator is the elevation of urinary hyaluronic acid levels, demonstrated in our patient and also observed in the phenotypically distinct Werner and Hutchinson-Gilford premature aging syndromes. On one hand, it could be argued that this supports the concept that premature aging syndromes exist as a biological continuum. On the other hand, it is equally valid to argue that syndromes of premature aging are so described merely because they include recognizable changes of normal aging and that the demonstration of an underlying mutation in a collagen gene, for example, invalidates their study as models of accelerated normal aging. © Wiley-Liss, Inc.     

Activation of mRNA expression of collagen,collagenase and its inhibitor on renal biopsy specimens in patients with IgA nephropathy

Summary: In situ hybridization of mRNA for collagen IV, collagen VI, stromelysin (MMP-3) and TIMP1 was examined in renal biopsy specimens from patients with IgA nephropathy (IgAN) or diabetic nephropathy with various degrees of tissue damage. The majority of cells in the glomeruli expressed these mRNA almost simultaneously, but a few cells demonstrated positive expression for only one of these probes. There was a parallel relationship between the degree of tissue damage and that of mRNA expressions of these probes in patients with IgAN, while patients with diabetic nephropathy showed a reverse relationship between these two parameters. It is concluded that patients with mesangial proliferative glomerulonephritis expressed mRNA for collagen collagenase and its inhibitor in the glomeruli in parallel with the progress of tissue damage. In contrast, glomerular samples from patients with diabetic nephropathy showed that there was an inverse relationship between tissue damage and expression of mRNA. It is concluded that expression of collagen, collagenase and its inhibitor parallels the progression of glomerular changes in IgAN, but such parallel expression was not observed in patients with diabetic nephropathy.