Geodiversity data for Europe.

Geodiversity is an essential part of nature's diversity. However, geodiversity is insufficiently understood in terms of its spatial distribution and its relationship to biodiversity over large spatial extents. Here, we present European geodiversity data at resolutions of 1 km and 10 km. We assess terrestrial geodiversity quantitatively as a richness variable (georichness) using a commonly employed grid-based approach. The data incorporate aspects of geological, pedological, geomorphological and hydrological diversity, which are also available as separate richness variables. To evaluate the data, we correlated European georichness with empirically tested national georichness data from Finland, revealing a positive correlation at both 1 km (rp = 0.37, p < 0.001) and 10 km (rp = 0.59, p < 0.001) resolutions. We also demonstrate potential uses of the European data by correlating georichness with vascular plant species richness in two contrasting example areas: Finland and Switzerland. The positive correlations between georichness and species richness in Finland (rp = 0.34, p < 0.001) and Switzerland (rp = 0.26, p < 0.001) further support the use of our data in geodiversity-biodiversity research. Moreover, there is great potential beyond geodiversity-biodiversity questions, as the data can be exploited across different regions, ecosystems and scales. These geodiversity data provide an insight on abiotic diversity in Europe and establish a quantitative large-scale geodiversity assessment method applicable worldwide. This article is part of the Theo Murphy meeting issue 'Geodiversity for science and society'.

Gait speed and one-leg standing time each add to the predictive ability of FRAX.

Gait speed or one-leg standing time (OLST) as additional predictors in FRAX. Population 351 elderly women followed 10 years. Both could improve predictions. The area under curve (AUC) for FRAX is 0.59, OLST is 0.69 and gait speed is 0.71. The net reclassification index (NRI) for classification to highest risk quartile or lowest three quartiles was 0.24 for gait speed and non-significant for OLST. INTRODUCTION: The risk of falls and bone strength are two main determinants of hip fracture risk. The fracture risk assessment tool FRAX, however, lacks direct measures of fall risk1. A short OLST and a slow gait speed are both fall-related risk factors for hip fractures. The aim of this study was to investigate whether the addition to FRAX of either gait speed or OLST could improve the predictive ability for hip fractures, compared to FRAX alone. METHODS: A population-based sample of 351 women aged between 69 and 79 years were tested for one-leg standing time with eyes open and mean gait speed over a 15 + 15-m walk. Fracture and mortality data were obtained from health care registers. RESULTS: The AUC for the receiver operating characteristic (ROC) increased from 0.61 to 0.71 when gait speed was added to FRAX. The AUC was 0.69 for OLST added to FRAX. The highest quartile of hip fracture risks according to FRAX had an absolute 10-year risk of ≥15%. The population was divided into one group with a hip fracture risk of ≥15% and one group with a fracture risk of <15%. NRI for addition of gait speed to FRAX was 0.24 (p = 0.023), while NRI was 0.08 (p = 0.544) for addition of OLST to FRAX. CONCLUSION: Gait speed tended to improve the predictive ability of FRAX more than OLST, but they both added value to FRAX.

Seclusion experienced by mental health professionals.

Seclusion in psychiatric inpatient care means confining service users in a locked room. Service users and staff seem to have different opinions on the usefulness of seclusion. This is possibly the first time when two mental health nurses went voluntarily into seclusion and reported their experiences. The nurses felt that the seclusion room was inhumane and proposed improvements to seclusion in general and to the seclusion facilities in particular. Seclusion in psychiatric hospital care refers to isolating a service user from other service users and staff, most often in a locked and unfurnished room. Service users' experiences of seclusion are mostly negative, and although some have seen a rationale for its use, mental health nurses should be encouraged to evaluate current seclusion practices from the service user's perspective. In this small-scale experiment, two mental health nurses were voluntarily secluded for 24 h. The aim was to explore the experience of being secluded, to understand and evaluate the impact of seclusion in greater detail, and to encourage discussion on one of the controversies in mental health nursing. To the best of our knowledge, this is the first attempt to evaluate the impact of seclusion based on mental health nurses' firsthand experiences. The nurses received usual seclusion treatment and described their experiences of this every 6 h. Based on the nurses' experiences, seclusion, even in voluntary, safe and planned circumstances, may increase anxiety and frustration. Seclusion was viewed negatively and the physical environment was considered inhumane. The nurses offered some practical suggestions for updating seclusion practices and re-designing seclusion facilities. Mental health nurses, who frequently decide on and invariably implement seclusion, are key to improving seclusion practices.

District nurses' perceptions of osteoporosis management: a qualitative study.

UNLABELLED: Underdiagnosis of osteoporosis is common. This study investigated Swedish district nurses' perceptions of osteoporosis management. They perceived the condition as having low priority, and the consequences of this perception were insufficient awareness of the condition and perceptions of bone-specific medication as unsafe. They perceived, though, competency when working with fall prevention. INTRODUCTION: Undertreatment of patients with osteoporosis is common. Sweden's medical care strategy dictates prioritisation of various conditions; while guidelines exist, osteoporosis is not prioritised. The aim of this study was to investigate district nurses' perceptions of osteoporosis management within Sweden's primary health care system. METHODS: Four semi-structured focus group interviews were conducted with 13 female district nurses. The interviews were analysed using thematic analysis. RESULTS: The overall theme was perceiving osteoporosis management as ambiguous. The themes were perceiving barriers and perceiving opportunities. These subthemes were linked to perceiving barriers: (i) insufficient procedures, lack of time and not aware of the condition; (ii) insufficient knowledge about diagnosis and about fracture risk assessment tools; (iii) low priority condition and unclear responsibility for osteoporosis management; and (iv) bone-specific medication was sometimes perceived to be unsafe. These subthemes were linked to perceiving opportunities: (i) professional competency when discussing fall prevention in home visit programs, (ii) willingness to learn more about osteoporosis management, (iii) collaboration with other professionals and (iv) willingness to identify individuals at high risk of fracture. CONCLUSIONS: Osteoporosis was reported, by the district nurses, to be a low-priority condition with consequences being unawareness of the condition, insufficient knowledge about bone-specific medications, fracture risk assessment tools and procedures. These may be some of the explanations for the undertreatment of osteoporosis. At the same time, the district nurses described competency performing the home visits, which emerged as an optimal opportunity to discuss fall prevention and to introduce FRAX with the aim to identify individuals at high risk of fracture.

One-leg standing time and hip-fracture prediction.

UNLABELLED: A hip fracture results in a lower quality of life and a cost of £30,000. In this study, one-leg standing time (OLST) had a negative linear relationship to the risk of a hip fracture. OLST could be a useful tool to assess the need for fracture-preventive interventions. INTRODUCTION: A hip fracture immobilizes, restricts autonomy, shortens life expectancy, and results in a cost of £30,000 in the UK health care system. However, effective preventive treatments can be offered to high-risk individuals. Impaired postural balance is an important risk factor for hip fractures, and the aim of this study was to evaluate whether OLST can predict hip fractures in elderly women. FRAX is the most established fracture risk assessment tool worldwide and a secondary aim was to relate the predictive ability of OLST to that of FRAX in this population. METHODS: Three hundred fifty-one women aged between 69 and 79 years were timed standing on one leg up to 30 s with eyes open and assessed with FRAX. Fracture data was obtained from registers. RESULTS: The main outcome, a hip fracture, occurred in 40 of the 351 participants (11.4%). The age-adjusted risk of a hip fracture was 5% lower with 1 s longer OLST (Hazard ratio 0.95, 95% CI 0.927-0.978). The relation between OLST and hip fracture risk was linear. Harrell's c was 0.60 for FRAX and 0.68 for OLST adjusted for age. CONCLUSION: With 1 s longer OLST, the risk of a hip fracture decreased significantly by 5%. This risk reduction was not explained by differences in the classic fracture risk factors included in FRAX. OLST had a predictive ability similar to FRAX. OLST is an easily performed balance test which may prove to be valuable in the assessment of hip fracture risk.

Mini nutritional assessment and 10-year mortality in free-living elderly women: a prospective cohort study with 10-year follow-up.

BACKGROUND/OBJECTIVES: Mini nutritional assessment (MNA) is the most frequently used screening test for malnutrition in elderly populations in continental Europe and Asia. Most studies on MNA's ability to predict mortality have only included persons admitted to hospital, living in nursing homes or at home with professional help with activities of daily living. The aim of this cohort study was to examine if MNA can predict 10-year mortality in the general elderly female population. SUBJECTS/METHODS: Of the 584 free-living elderly women invited, 351 agreed to participate and were tested with MNA between 1999 and 2000. A 10-year follow-up was conducted in 2010 with dates of death obtained from the Swedish death register. RESULTS: Participants whose MNA score was ≤ 23.5 points at inclusion had a significantly higher age-adjusted 10-year mortality risk than participants with a MNA score of >23.5 points. The hazard ratio was 2.36 (95% confidence interval 1.25-4.46), P <0.01. CONCLUSIONS: Participants with a MNA score, indicating an increased risk for malnutrition, were more than twice as likely to die during the 10-year follow-up as participants whose MNA score indicated normal nutritional status. Hence, MNA can predict mortality in a general, free-living, elderly female population.

Infant brain responses associated with reading-related skills before school and at school age.

INTRODUCTION: In Jyväskylä Longitudinal Study of Dyslexia, we have investigated neurocognitive processes related to phonology and other risk factors of later reading problems. Here we review studies in which we have investigated whether dyslexic children with familial risk background would show atypical auditory/speech processing at birth, at six months and later before school and at school age as measured by brain event-related potentials (ERPs), and how infant ERPs are related to later pre-reading cognitive skills and literacy outcome. PATIENTS AND METHODS: One half of the children came from families with at least one dyslexic parent (the at-risk group), while the other half belonged to the control group without any familial background of dyslexia. RESULTS: Early ERPs were correlated to kindergarten age phonological processing and letter-naming skills as well as phoneme duration perception, reading and writing skills at school age. The correlations were, in general, more consistent among at-risk children. Those at-risk children who became poor readers also differed from typical readers in the infant ERP measures at the group level. ERPs measured before school and at the 3rd grade also differed between dyslexic and typical readers. Further, speech perception at behavioural level differed between dyslexic and typical readers, but not in all dyslexic readers. CONCLUSIONS: These findings suggest persisting developmental differences in the organization of the neural networks sub-serving auditory and speech perception, with cascading effects on later reading related skills, in children with familial background for dyslexia. However, atypical auditory/speech processing is not likely a sufficient reason by itself for dyslexia but rather one endophenotype or risk factor.

The role of IGF-I and IGFBP-1 status and secondary hyperparathyroidism in relation to osteoporosis in elderly Swedish women.

UNLABELLED: IGFBP-1 showed a strong inverse relation to the BMD values. The IGF-I values had a significant positive relation to the BMD values at all sites with the exception of the lumbar spine. The use of loop diuretics was a more important cause of secondary hyperparathyroidism than vitamin D status. INTRODUCTION: Our aim was to investigate among elderly women the relationship to osteoporosis of calcium-regulating hormones and insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-1 (IGFBP-1). METHODS: A population-based cross-sectional study of 350 elderly women (mean age 73 years). Measurements of bone mineral density (BMD) of the left hip, lumbar spine and heel and risk markers for osteoporosis were studied. RESULTS: The BMD values showed significant inverse relationship with the values of IGFBP-1 at all sites of measurement and significant positive relationship with the values of IGF-I at all sites with the exception of the lumbar spine. There was no significant association between the values of BMD and the values of 25-hydroxy vitamin D (25(OH)D). The use of loop diuretics was strongly and significantly associated with elevated levels of PTH >65 pg/ml (OR 4.4, P < 0.001). CONCLUSIONS: The anabolic growth factor IGF-I and its modulating binding protein IGFBP-1 showed a stronger association with the BMD values than the calcium regulating hormones 25(OH)D and PTH. In this study the use of loop diuretics was a more important cause of secondary hyperparathyroidism than vitamin D status.

Nutritional status, as determined by the Mini-Nutritional Assessment, and osteoporosis: a cross-sectional study of an elderly female population.

OBJECTIVE: To investigate the relationship between osteoporosis and nutritional status as determined by the Mini-Nutritional Assessment (MNA). DESIGN: A cross-sectional study. SETTING: Stockholm, Sweden. SUBJECTS: A total of 351 elderly free-living women (mean age 73+/-2.3 years). METHODS: MNA (range 0-30 points; <17 indicates malnutrition, 17.5-23.5 risk of malnutrition and >or=24 well nourished), measurements of bone mineral density of the left hip and lumbar spine using Hologic QDR 4500, and of the heel using Calscan DEXA-T. RESULTS: The median MNA score was 27 (range 12.5-30). One woman was classified as malnourished and 7.4% were at risk of malnutrition. Osteoporosis of the femoral neck was observed in 22% and a fracture after the age of 50 was reported by 31% of the participants. The following items in the MNA questionnaire exhibited an increased risk of having osteoporosis in the femoral neck and/or total hip: an MNA score of <27 (odds ratio (OR)=2.09; CI=1.14-3.83); a mid-arm circumference of less than 28 cm (OR=2.97; CI=1.29-6.81); and regular use of more than 3 drugs each day (OR=2.12; CI=1.00-4.50). A body weight of more than 70 kg exhibited a decreased risk of having osteoporosis (OR=0.31; CI=0.14-0.70). CONCLUSIONS: In general, the nutritional status was good in this population of free-living elderly women. Nevertheless, half of the women who displayed an MNA score <27 points had a twofold increased risk of having osteoporosis. SPONSORSHIP: Karolinska Institutet, Stockholm County Council.

Bone mineral density measurement in the calcaneus with DXL: comparison with hip and spine measurements in a cross-sectional study of an elderly female population.

We investigated the relationship between calcaneal and axial bone mineral density in an elderly female population. We also investigated the influence of changing the reference populations on T-score values. Bone mineral density (BMD) was determined in 388 women (mean age 73 years) participating in a cross-sectional study. BMD values were determined at the left hip and the lumbar spine, L1-L4, using Hologic QDR 4500 equipment for dual X-ray absorptiometry (DXA). The calcaneal measurements were made with DEXA-T, a device using a dual X-ray and laser (DXL) technique that combines DXA measurement with measurement of the heel thickness using a laser reflection technique. DEXA-T is an older version of the Calscan DXL device now commercially available. T-score values were calculated for hip measurements with both the original reference population of the Hologic device and the NHANES III reference population. T scores for heel measurements were calculated with the original reference population of the peripheral device and the Calscan database, a new calcaneal reference population. Changing the reference populations had a great influence on both the heel and the hip T scores, especially those of the femoral neck where the percentage of subjects identified as osteoporotic decreased from 53% to 23%. We conclude that, with the NHANES III and the larger Calscan database, using the cut-off point of -2.5 SD, the heel measurements had optimal accuracy for detecting osteoporosis at either the combination of the lumbar spine and the femoral neck or the combination of the lumbar spine, the femoral neck, the total hip and the trochanter. BMD measurements of the calcaneus with DXL correlated fairly well with measurements at axial sites at the group level, while in individual subjects large deviations were observed between all the measured sites. We also conclude that the influence of the reference populations on the T scores is substantial when different DXA methods are being compared; the total number of subjects classified as osteoporotic varied from 7% to 53% between the sites and with different reference populations.

Up regulation of cathepsin K expression in articular chondrocytes in a transgenic mouse model for osteoarthritis.

OBJECTIVES: To study the expression of cysteine proteinases, particularly cathepsin K, and their extracellular inhibitor cystatin C in articular cartilage of transgenic Del1 mice which harbour a short deletion mutation in a type II collagen transgene and are predisposed to early onset osteoarthritis. METHODS: Northern analysis was used to measure mRNA levels of cathepsins B, H, K, L, and S, and cystatin C in total RNA extracted from knee joints of Del1 mice, using their non-transgenic litter mates as controls. Immunohistochemistry and morphometry was used to study the distribution of cathepsin K and cystatin C in the knee joints. RESULTS: Up regulation of cathepsin K mRNA expression was seen in the knee joints of transgenic Del1 mice at the onset of cartilage degeneration. Cathepsin K was found near sites of matrix destruction in articular chondrocytes, particularly in clusters of proliferating cells, and in calcified cartilaginous matrix. In intact articular cartilage of control animals, cathepsin K was only seen in a small number of chondrocytes. Upon aging, control animals also developed osteoarthritis, which was accompanied by increased cathepsin K expression. Cystatin C was mostly localised in and around chondrocytes located in calcified cartilage, with no obvious association with the onset of cartilage degeneration. CONCLUSION: The temporospatial distribution of cathepsin K in osteoarthritic cartilage suggests a role for this enzyme in the pathogenesis of osteoarthritis. Because cathepsin K can digest cartilage matrix components it may contribute to the development of osteoarthritic lesions. These data may provide new clues for the development of treatments aimed at preventing cartilage degeneration.

Chicken B-cell-activating factor: regulator of B-cell survival in the bursa of fabricius.

Previous studies on mammals have demonstrated that a tumour necrosis factor family member, B-cell-activating factor (BAFF) (BlyS, TALL-1), is mainly produced by myeloid and dendritic cells and that BAFF promotes B-cell differentiation and survival in a paracrine fashion. We have recently shown that BAFF is upregulated at the bursal stage of the avian B-cell development. We now show that the avian bursal B cells and B-cell lines, RP-9, RP-13 and DT40, express chicken BAFF (cBAFF). In situ hybridization confirms strong cBAFF expression within the bursal follicles. Like mammals, cBAFF is expressed in the avian myeloblast and myelomonocytic cell lines but not in the peripheral blood alphabeta and gammadelta T cells. The binding of recombinant human BAFF (hBAFF) to the bursal B-cells indicates a conserved receptor-ligand binding. Furthermore, the recombinant hBAFF has a positive effect on bursal cell proliferation and transiently inhibits cell death in vitro. In conclusion, cBAFF is highly conserved structurally, but as a novel observation we suggest cBAFF to function in an autocrine fashion to promote the growth and maturation of follicular B cells in bursa of Fabricius.

Transgenic mouse models for studying the role of cartilage macromolecules in osteoarthritis.

The development of transgenic technology has made possible the generation of targeted gene-mutated mouse lines suitable for use in experimental osteoarthritis (OA) research. Transgenic mice harbouring mutations in cartilage collagen types II and IX develop early-onset OA and are therefore promising models of age-related OA, even though the mice often show signs of chondrodysplasia. Also, mouse lines harbouring other engineered mutations of the extracellular molecules have given rise to early OA. The molecular background of a few spontaneous mutations in mice has also been clarified and the characterization of the OA phenotype is now in progress. These mutations cause severe chondrodysplasia and death in homozygous mice, but the heterozygous offspring develop the early-onset OA phenotype.

Differential expression patterns of matrix metalloproteinases and their inhibitors during development of osteoarthritis in a transgenic mouse model.

OBJECTIVE: To characterise the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) during degeneration of articular cartilage in a transgenic Del1 mouse model for osteoarthritis. METHODS: Northern analysis was used to measure mRNA levels of MMP-2, -3, -8, -9, -13, and -14, and TIMP-1, -2, and -3 in total RNA extracted from knee joints of transgenic Del1 mice, harbouring a 15 amino acid deletion in the triple helical domain of the alpha1(II) collagen chain, using their non-transgenic littermates as controls. Immunohistochemistry was used to study the presence of cleavage products (neoepitopes) of type II collagen, and the distribution of MMP-13 and TIMP-1 in degenerating cartilage. RESULTS: Each of the MMP and TIMP mRNAs analysed exhibited distinct expression patterns during development and osteoarthritic degeneration of the knee joint. The most striking change was up regulation of MMP-13 mRNA expression in the knee joints of Del1 mice at the onset of cartilage degeneration. However, the strongest immunostaining for MMP-13 and its inhibitor TIMP-1 was not seen in the degenerating articular cartilage but in synovial tissue, deep calcified cartilage, and subchondral bone. The localisation of type II collagen neoepitopes in chondrocytes and their pericellular matrix followed a similar pattern; they were not seen in cartilage fibrillations, but in adjacent unaffected cartilage. CONCLUSION: The primary localisation of MMP-13 and TIMP-1 in hyperplastic synovial tissue, subchondral bone, and calcified cartilage suggests that up regulation of MMP-13 expression during early degeneration of articular cartilage is a secondary response to cartilage erosion. This interpretation is supported by the distribution of type II collagen neoepitopes. Synovial production of MMP-13 may be related to removal of tissue debris released from articular cartilage. In the deep calcified cartilage and adjacent subchondral bone, MMP-13 probably participates in tissue remodelling.

Expression of Sox9 and type IIA procollagen during ocular development and aging in transgenic Del1 mice with a mutation in the type II collagen gene.

PURPOSE: To study the expression and distribution of transcription factor Sox9 and type IIA procollagen in the developing and aging eyes of normal and transgenic Dell mice carrying pro(alpha)1(II) collagen transgenes with a short deletion mutation, which cause ocular abnormalities in this mouse line. METHODS: The eyes of Del1 mice were studied on embryonic days E14.5, E16.5 and E18.5, and at the ages of 4 and nine months, using their nontransgenic littermates as controls. Sox9 and pro(alpha)1(IIA) collagen were detected by RNase protection assay and immunohistochemistry. RESULTS: RNase protection assay revealed Sox9 transcripts in the eyes of Del1 and control mice during development and aging. The mRNA for type IIA procollagen had a similar temporal expression pattern. On embryonic days E14.5, E16.5 and E18.5, Sox9 was located by immunohistochemistry in the nuclei and type IIA procollagen in the extracellular space of the developing retina. During growth and aging, the ocular expression of Sox9 mRNA and the immunohistochemical reaction for Sox9 antibody diminished, concomitant with the reduction in type II procollagen mRNA. However, at the age of nine months, levels of Sox9 and type IIA procollagen mRNAs were higher in the degenerating eyes of Del1 and control mice. CONCLUSIONS: The similarities in the temporo-spatial distribution of Sox9 and type IIA procollagen suggest that this transcription factor is involved in the activation of type II collagen expression in the eye, as has been demonstrated in prechondrogenic mesenchyme and immature cartilage. The increased production of Sox9 and type IIA procollagen in the aging retina and vitreous is analogous to degenerating articular cartilage where attempted tissue repair has also been observed.

Activation of chondrogenesis in response to injury in normal and transgenic mice with cartilage collagen mutations.

OBJECTIVE: The aim of this report is to describe and discuss the reparative capacity of articular cartilage by focusing on similarities and differences in the activation of chondrogenesis in adult bone and cartilage in response to injury. DESIGN: The present report describes three different models of skeletal repair in the mouse. Two of the models deal with bone healing, where the activation of chondrogenesis and formation of callus tissue is greatly dependent on the rigidity of fixation. The third comprises two transgenic mouse models for osteoarthritis where dominant negative mutations in cartilage-specific genes disturb the structural integrity of the cartilage collagen fibrils. RESULTS: Molecular biologic and immunohistochemical analyses demonstrated that activation of chondrogenesis in healing fractures, i.e., activation and maintenance of the chondrocyte phenotype was preceded by increased production and nuclear accumulation of transcription factor SOX9. A similar, albeit smaller, chondrogenic response was observed during healing of biomechanically stable metaphyseal bone defects. In degenerating articular cartilage of transgenic mice, however, the production of cartilage-specific collagen types and SOX9 was markedly reduced upon aging which probably explains why repair of cartilage defects was insufficient. CONCLUSION: Understanding of the molecular mechanisms involved in successful and unsuccessful activation of chondrogenesis during skeletal repair, will provide information needed for enhancement of the chondrocytic response at sites of skeletal repair. Our data also demonstrates that specific effector molecules can be efficiently introduced into chondrocytes and their precursors by adenovirus-mediated gene transfer.

Murine fibromodulin: cDNA and genomic structure, and age-related expression and distribution in the knee joint.

The genomic structure of murine fibromodulin was determined, and its age-related expression and distribution were characterized in knee epiphyses, with decorin studied for reference. Fibromodulin, as well as decorin, have roles in collagen fibrillogenesis both in vitro and in vivo. The murine fibromodulin gene, Fmod, was similar with that in other species, with three exons and 86% of the translated sequence in exon 2. The 2.7 kb long cDNA contains an open reading frame of 1131 nt. Fibromodulin mRNA levels were highest in tissues rich in fibrillar collagens type I or type II. During growth, the distribution of fibromodulin mRNA was similar with that of type II collagen, with the highest levels between 5 days and 1 month of age. Thereafter, the expression of type II collagen declined to a level near the detection limit, whereas the fibromodulin expression decreased less markedly to a level of approx. 35% of maximum, and remained constant throughout the rest of the observation period. In contrast, decorin mRNA levels were the highest in old animals. Pericellular deposition of fibromodulin was strong around the late-hypertrophic chondrocytes of the secondary ossification centre and in the growth plate. In young epiphyses, both fibromodulin and decorin were found interterritorially, mainly in the uncalcified and deep-calcified cartilage. In the old mice, calcified cartilage became enriched with regard to fibromodulin, while, in contrast, decorin deposition diminished, particularly near the tidemark. In the subchondral bone trabeculae, decorin was found in the endosteum of growing, but not in the mature, epiphyses. Differences in the expression and distribution profiles suggest different roles for fibromodulin and decorin in the regulation of collagen fibrillogenesis, maintenance of the fibril organization and matrix mineralization. As fibromodulin is deposited closer to cells than decorin, it may have a primary role in collagen fibrillogenesis, whereas decorin might be involved in the maintenance of fibril structures in the interterritorial matrix.

Expression of Sox9 and type IIA procollagen during attempted repair of articular cartilage damage in a transgenic mouse model of osteoarthritis.

OBJECTIVE: To determine the capacity of chondrocytes in aging and degenerating articular cartilage to produce major components of the extracellular matrix and maintain the normal structure of articular cartilage in a transgenic mouse model of osteoarthritis. METHODS: Transcription factor Sox9 was used as an indicator of the activation and maintenance of the articular chondrocyte phenotype. Knee joints of Del1 mice carrying 6 copies of the pro alpha1(II) collagen transgene with a short deletion mutation were analyzed at the age of 10 days and at 2, 3, 4, 6, 9, and 15 months by Northern hybridization, RNase protection assay, quantitative reverse transcription-polymerase chain reaction, and immunohistochemistry. Nontransgenic littermates were used as controls. RESULTS: We demonstrated the presence of Sox9 in articular chondrocytes during development, growth, and aging, with the highest messenger RNA levels during the period of rapid growth. With the appearance of degenerative lesions in articular cartilage, 2 repair processes were observed. Local proliferation and activation of chondrocytes rich in Sox9, surrounded by type IIA procollagen and proteoglycans, was seen in articular cartilage. In contrast, metabolically inactive chondrocytes were observed at the margins of the defects. They were devoid of Sox9 and were surrounded by a proteoglycan-poor matrix. Sometimes, the lesions were filled with repair tissue that contained type III collagen but little proteoglycan or type II collagen. CONCLUSION: The results indicate that chondrocytes in mature articular cartilage are capable of inducing the production of Sox9 and type IIA procollagen, which is typical of early chondrogenesis. Degenerative defects in the knee joints of transgenic Del1 mice are associated with local activation of chondrocytes, which probably contributes to the repair process. In other areas, the repair process produces a noncartilaginous matrix, which is insufficient to maintain the integrity of articular cartilage and which allows degeneration to proceed.

Age-dependent changes in the expression of matrix components in the mouse eye.

Although the presence of 'cartilage-specific' collagens in the eye has been documented earlier, very little is known about their synthesis rates during ocular development, growth and aging. The purpose of the present study was to follow changes in the mRNA levels and distribution of key components of the extracellular matrix in the eyes of normal and transgenic Del1 mice, harboring a short deletion mutation in the type II collagen gene, during ocular growth and aging. Total RNAs extracted from mouse eyes were studied by Northern analysis for mRNA levels of type I, II, III, VI, IX and XI collagens, biglycan, fibromodulin and decorin. A predominant finding of the present study was the marked reduction in the mRNA levels of type I and II collagens in the eye upon aging. The changes in the mRNA levels of type III and VI collagen and proteoglycans were smaller. Localization of type II and IX collagen in the eye was performed by immunohistochemistry. Despite the reduction in the type II collagen mRNA levels, immunohistochemistry confirmed widespread distribution of the protein also in aging mouse eyes, suggesting its slow turnover. Although the Del1 mutation caused gradual degenerative lesions in the eyes, the distribution of the protein remained essentially unchanged. The widespread distribution and marked downregulation of type II collagen production in the mouse eye upon aging probably explain the gradual development of degenerative lesions, particularly in the eyes of transgenic Del1 mice, where production of mutant type II collagen chains also contributes to the process.