The disability associated with hand osteoarthritis is substantial in a cohort of post-menopausal women: the QUALYOR study.

OBJECTIVES: Our primary aims were to assess current prevalence of HOA and the disability associated with this condition, in the group usually most affected, i.e., women older than 55. METHODS: We performed hand radiographs, clinical examination, grip strength measurement, AUSCAN and COCHIN questionnaires in a cohort of postmenopausal women aged at least 55. Radiographic hand OA (RHOA) was defined as at least 2 affected joints among 30, grading 2 or more using the Kellgren Lawrence score but without any HOA symptom. Symptomatic HOA (OA ACR) was defined according to ACR criteria for hand OA. Moderate to severe symptomatic HOA was defined as having OA ACR and AUSCAN total score of >43/100. RESULTS: We enrolled 1,189 participants. The mean age was 71.7 years. Inter-reader reliability of radiographs reading was good (ICC = 0.86) and intra-reader reliability was excellent (ICC = 0.97). Among the 1,189 women, 333 (28.0%) had RHOA, 482 (40.5%) patients fulfilled the ACR criteria for symptomatic HOA and 82 of these (17% of OA ACR population) had moderate to severe symptomatic HOA. The prevalence of symptomatic erosive osteoarthritis was 11.8%. Mean AUSCAN and Cochin scores were higher and grip strength lower in patients with symptomatic HOA compared to patient without HOA. Differences were more noticeable in patients with moderate to severe HOA. CONCLUSIONS: We have assessed disability associated with HOA in greater detail than previously and found that a third of postmenopausal women had RHOA, two fifths had symptomatic HOA and one sixth of symptomatic patients had moderate to severe HOA related disability and a tenth had symptomatic erosive osteoarthritis, representing a substantial burden of disease in our population-based cohort.

Interventions to improve osteoporosis care: a systematic review and meta-analysis.

Osteoporosis (OP) is a major public health concern, but still OP care does not meet guidelines. Interventions have been developed to improve appropriate OP management. The objective of the present study was to systematically review the current literature to ascertain the efficacy of interventions to improve OP care and characterize interventions taking into account elements related to their potential cost and feasibility. Studies published from 2003 to 2018 were retrieved from PubMed/MEDLINE, Science Direct, Web of Science, Cochrane, and Wiley Online Library databases. Screening of references and quality assessment were independently performed by two reviewers. We classified interventions into three types according to the target of the intervention: health system (structural interventions), healthcare professional (HCP), and patient. Meta-analysis was performed by type of intervention and their effect on two outcomes: prescription of BMD measurement and prescription of OP therapy. A total of 4268 records were screened; 32 studies were included in the qualitative analysis and 29 studies in the quantitative analysis. Structural interventions strongly and significantly improved prescription of BMD measurement (OR = 9.99, 95% CI 2.05; 48.59) and treatment prescription (OR = 3.82, 95% CI 2.16; 6.75). The impact of HCP-centered interventions on BMD measurement prescription did not reach statistical significance (OR = 2.19, 95% CI 0.84; 5.73) but significantly improved treatment prescription (OR = 3.82, 95% CI 2.16; 6.75). Interventions involving patients significantly improved the prescription of BMD measurement (OR = 2.16, 95% CI 1.62; 2.89) and treatment prescription (OR = 1.70, 95% CI 1.35; 2.14). Interventions to improve OP management had a significant positive impact on prescription of BMD measurement but a more limited impact on treatment prescription.

Osteoporosis prevention: where are the barriers to improvement in a French general population? A qualitative study.

We conducted a qualitative study with French men and women in order to provide insight into individuals' experiences, behaviors, and perceptions about osteoporosis (OP) and OP care. The data showed that both sexes, but especially men, were unfamiliar with OP, did not always feel concerned, and mistrusted pharmacological treatments. INTRODUCTION: To engage actively in osteoporosis (OP) prevention, people need to have basic knowledge about the disease. The aim of this qualitative study was to explore knowledge and representations of OP care and prevention among both men and women. METHODS: Focus groups were conducted in the Rhône-Alpes Region, France, with women aged 50-85 years and men aged 60-85 years, with or without a history of fragility fracture and/or an OP diagnosis (respectively referred to as "aware" or "unaware"). A total of 45 women (23 "aware" and 22 "unaware" in 5 and 4 focus groups, respectively) and 53 men (19 "aware" and 34 "unaware" in 3 and 4 focus groups, respectively) were included. A thematic analysis of transcripts was performed to explore knowledge and representations about OP, risk factors, prevention, and treatment. RESULTS: The data showed that both sexes, but especially men, had limited knowledge of OP and considered it as a natural aging process not related to fragility fractures. They generally did not feel concerned by OP and no important difference was observed between "aware" and "unaware" patients. Women expressed their fear of the disease, associated with aging and the end of life, while men considered it to be a women's disease only. Both sexes were aware of OP risk factors, but were suspicious towards treatments because of the associated side effects. CONCLUSION: Understanding people's representation of OP might help to provide patients with relevant information in order to optimize their preventive behavior and decrease the burden of the disease.

Post-fracture care: do we need to educate patients rather than doctors? The PREVOST randomized controlled trial.

We conducted a multicenter, randomized controlled trial to evaluate the impact of a population-based patient-centered post-fracture care program with a dedicated case manager, PREVention of OSTeoporosis (PREVOST), on appropriate post-fracture osteoporosis management. We showed that, compared to usual care, BMD investigation post-fracture was significantly improved (+20%) by our intervention program. INTRODUCTION: Our study aims to evaluate the impact of a population-based patient-centered post-fracture care program, PREVOST, on appropriate post-fracture care. METHODS: Multicenter, randomized controlled trial enrolling 436 women aged 50 to 85 years and attending a French hospital, for a low-energy fracture of the wrist or humerus. Randomization was stratified by age, hospital department, and site of fracture. The intervention was performed by a trained case manager who interacted only with the patients, with repeated oral and written information about fragility fractures and osteoporosis management, and prompting them to visit their primary care physicians. Control group received usual care. The primary outcome was the initiation of an appropriate post-fracture care defined by Bone Mineral Density (BMD) and/or anti-osteoporotic treatment prescription at 6 months. RESULTS: At 6 months, 53% of women in intervention group initiated a post-fracture care versus 33% for usual care (adjOR 2.35, 95%CI [1.58-3.50], p < 0.001). Post-fracture care was more frequent after wrist than humerus fracture (adjOR 1.93, 95%CI [1.14-3.30], p = 0.015) and decreased with age (adjOR for 10 years increase 0.76, 95%CI [0.61-0.96], p = 0.02). The intervention resulted in BMD prescription in 50% of patients (adjOR 2.10, 95%CI [1.41-3.11], p < 0.001) and in BMD performance in 41% of patients (adjOR 2.12, 95%CI [1.40-3.20], p < 0.001) versus 33 and 25% for usual care, respectively. Having performed a BMD increased treatment prescription; however, only 46% of women with a low BMD requiring a treatment according to the French guidelines received a prescription. CONCLUSION: A patient-centered care program with a dedicated case manager can significantly improve post-fracture BMD investigation.

[Nutrition and age-related macular degeneration]. / Nutrition et dégénérescence maculaire liée à l'âge.

Age-related macular degeneration (AMD) is the leading cause of vision loss in France and in other industrialized countries. AMD affects around 20 % of the population over the age of 80 years. This complex and multifactorial disease involves both genetic susceptibility and environmental factors. Smoking and nutrition are well-known modifiable risk factors for AMD. Numerous studies provide convincing arguments in favor of micronutrients to encourage dietary advice and the prescription of nutritional supplements containing antioxidant vitamins, lutein and omega-3 fatty acids. Attention to modifiable risk factors is of utmost importance to reduce progression to advanced AMD and associated medical and societal burdens.

Value of rare diseases reference centers: impact on diagnosis and access to specialized care in fibrous dysplasia of bone.

INTRODUCTION: Reference Centers and Rare Disease Health Networks aim to improve the management of patients with rare diseases. The French reference center for Fibrous Dysplasia was certified in 2006. OBJECTIVE: The objective of our study was to assess the effectiveness of our reference center since its constitution. METHODS: In a retrospective cohort study, we compared the activity of our center, including the time elapsed between access to the center and the diagnostic delay of patients with Fibrous Dysplasia between two periods, 1994-2006 (before certification) and 2007-2019 (after certification). Data were extracted from patients' records (Easily®). Wilcoxon and Fisher tests were performed, using R®. RESULTS: Our cohort included 527 patients with Fibrous Dysplasia/Mc Cune Albright syndrome. The activity of the Fibrous Dysplasia center increased from 139 patients in the first period (1994-2006) to an additional 388 patients for the second period (2007-2019). Mean time elapsed to diagnosis of Fibrous Dysplasia was 1.5 years before 2007 and 1.9 years after 2007 (p = 0.12). Diagnosis was made before referral in over 80% of patients. There was a non-significant decrease in the number of patients with delayed diagnosis: 37 patients (44%) in the first period had a diagnostic delay and 94 patients (33%) in the second period (p = 0.07). Patients were referred to our center on average 6.8 years (before 2007) and 7.9 years (after 2007) after their diagnosis (p = 0.77). CONCLUSION: Healthcare organization with reference centers significantly impacted the management of patients with Fibrous Dysplasia/Mc Cune Albright syndrome, with a substantial increase in the activity of our center, that roughly tripled since certification. This healthcare organization was also associated with a trend toward decreasing diagnostic delay. However, diagnostic delay affected more than a third of patients and the time to access to the center remained extended (≈7-8 years after diagnosis). The current challenge lies in informing primary care providers and patients about education to rare diseases and existence of reference centers for earlier and more effective specialized management.

The multiple facets of periostin in bone metabolism.

Periostin is a matricellular glutamate-containing protein expressed during ontogenesis and in adult connective tissues submitted to mechanical strains including bone and, more specifically, the periosteum, periodontal ligaments, tendons, heart valves, or skin. It is also expressed in neoplastic tissues, cardiovascular and fibrotic diseases, and during wound repair. Its biological functions are extensively investigated in fields such as cardiovascular physiology or oncology. Despite its initial identification in bone, investigations of periostin functions in bone-related physiopathology are less abundant. Recently, several studies have analyzed the potential role of periostin in bone biology and suggest that periostin may be an important regulator of bone formation. The aim of this article is to provide an extensive review on the implications of periostin in bone biology and its potential use in benign and metabolic bone diseases.

Genome wide signatures of positive selection: the comparison of independent samples and the identification of regions associated to traits.

BACKGROUND: The goal of genome wide analyses of polymorphisms is to achieve a better understanding of the link between genotype and phenotype. Part of that goal is to understand the selective forces that have operated on a population. RESULTS: In this study we compared the signals of selection, identified through population divergence in the Bovine HapMap project, to those found in an independent sample of cattle from Australia. Evidence for population differentiation across the genome, as measured by FST, was highly correlated in the two data sets. Nevertheless, 40% of the variance in FST between the two studies was attributed to the differences in breed composition. Seventy six percent of the variance in FST was attributed to differences in SNP composition and density when the same breeds were compared. The difference between FST of adjacent loci increased rapidly with the increase in distance between SNP, reaching an asymptote after 20 kb. Using 129 SNP that have highly divergent FST values in both data sets, we identified 12 regions that had additive effects on the traits residual feed intake, beef yield or intramuscular fatness measured in the Australian sample. Four of these regions had effects on more than one trait. One of these regions includes the R3HDM1 gene, which is under selection in European humans. CONCLUSION: Firstly, many different populations will be necessary for a full description of selective signatures across the genome, not just a small set of highly divergent populations. Secondly, it is necessary to use the same SNP when comparing the signatures of selection from one study to another. Thirdly, useful signatures of selection can be obtained where many of the groups have only minor genetic differences and may not be clearly separated in a principal component analysis. Fourthly, combining analyses of genome wide selection signatures and genome wide associations to traits helps to define the trait under selection or the population group in which the QTL is likely to be segregating. Finally, the FST difference between adjacent loci suggests that 150,000 evenly spaced SNP will be required to study selective signatures in all parts of the bovine genome.

Serum periostin levels and severity of fibrous dysplasia of bone.

Fibrous dysplasia of bone (FD) is a rare congenital bone disease, characterized by a fibrous component in the bone marrow. Periostin has been extensively researched because of its implication in various fibrotic or inflammatory diseases. Periostin may be associated with the burden or the severity of FD. The case control PERIOSDYS study aimed at assessing serum periostin levels in FD patients. Sixty four patients with monostotic or polyostotic disease were included, in order to evaluate whether the concentrations were greater in patients than in 128 healthy age, BMI and sex-matched controls and if they were more elevated in patients with the more severe phenotypes. We found that periostin levels were greater in patients with FD compared to controls (mean = 1085 vs 958 pmol/l, p = 0.026), especially in those with a history of fracture (mean = 1475 vs 966 pmol/l, p = 0.0005), polyostotic forms (mean = 1214 vs 955 pmol/l, p = 0.004) or McCune-Albright syndrome (mean = 1585 vs 1023 pmol/l, p = 0.0048). In contrast, high pain levels were not associated with periostin levels (mean = 1137 vs 1036 pmol/l, p = 0.445). Furthermore, patients undergoing bisphosphonate therapy had significantly lower levels than treatment naïve patients (mean = 953 vs 1370 pmol/l, p = 0.002). In conclusion, periostin may be a biochemical marker indicative of the most severe forms of FD and could be used to monitor patients treated with bisphosphonates.

Variation at the Calpain 3 gene is associated with meat tenderness in zebu and composite breeds of cattle.

BACKGROUND: Quantitative Trait Loci (QTL) affecting meat tenderness have been reported on Bovine chromosome 10. Here we examine variation at the Calpain 3 (CAPN3) gene in cattle, a gene located within the confidence interval of the QTL, and which is a positional candidate gene based on the biochemical activity of the protein. RESULTS: We identified single nucleotide polymorphisms (SNP) in the genomic sequence of the CAPN3 gene and tested three of these in a sample of 2189 cattle. Of the three SNP genotyped, the CAPN3:c.1538+225G>T had the largest significant additive effect, with an allele substitution effect in the Brahman of alpha = -0.144 kg, SE = 0.060, P = 0.016, and the polymorphism explained 1.7% of the residual phenotypic variance in that sample of the breed. Significant haplotype substitution effects were found for all three breeds, the Brahman, the Belmont Red, and the Santa Gertrudis. For the common haplotype, the haplotype substitution effect in the Brahman was alpha = 0.169 kg, SE = 0.056, P = 0.003. The effect of this gene was compared to Calpastatin in the same sample. The SNP show negligible frequencies in taurine breeds and low to moderate minor allele frequencies in zebu or composite animals. CONCLUSION: These associations confirm the location of a QTL for meat tenderness in this region of bovine chromosome 10. SNP in or near this gene may be responsible for part of the overall difference between taurine and zebu breeds in meat tenderness, and the greater variability in meat tenderness found in zebu and composite breeds. The evidence provided so far suggests that none of these tested SNP are causative mutations.

Applications and implications of advances in human genetics: perspectives from a group of Black Americans.

OBJECTIVES: We explored the opinions of 40 Black Americans regarding: (1) what they thought most Blacks and Whites believe about genetic causes for perceived race differences in human traits, and (2) the impact of genetic science on them, their families, and Black people. METHODS: We conducted in-depth telephone interviews with 40 self-identified Black men and women. Transcripts of the interviews were recorded and examined for common themes. RESULTS: The majority of our respondents felt that most Whites, unlike most Blacks, attribute differences between these groups to genetic factors. Many in our sample felt that genetic advances may provide benefits in the area of health care, but many also recognized potential harm. CONCLUSIONS: Our results provide a glimpse as to what some Blacks believe about genetic science in the context of racial issues.

A flexible method for the preparation of thin film samples for in situ TEM characterization combining shadow-FIB milling and electron-beam-assisted etching.

A new method for the preparation of freestanding thin film samples for mechanical testing in transmission electron microscopes is presented. It is based on a combination of focused ion beam (FIB) milling and electron-beam-assisted etching with xenon difluoride (XeF2) precursor gas. The use of the FIB allows for the target preparation of microstructural defects and enables well-defined sample geometries which can be easily adapted in order to meet the requirements of various testing setups. In contrast to existing FIB-based preparation approaches, the area of interest is never exposed to ion beam irradiation which preserves a pristine microstructure. The method can be applied to a wide range of thin film material systems compatible with XeF2 etching. Its feasibility is demonstrated for gold and alloyed copper thin films and its practical application is discussed.

Experiences in Engaging the Public on Biotechnology Advances and Regulation.

Public input is often sought as part of the biosafety decision-making process. Information and communication about the advances in biotechnology are part of the first step to engagement. This step often relies on the developers and introducers of the particular innovation, for example, an industry-funded website has hosted various authorities to respond to questions from the public. Alternative approaches to providing information have evolved, as demonstrated in sub-Saharan Africa where non-governmental organizations and associations play this role in some countries and subregions. Often times, those in the public who choose to participate in engagement opportunities have opinions about the overall biosafety decision process. Case-by-case decisions are made within defined regulatory frameworks, however, and in general, regulatory consultation does not provide the opportunity for input to the overall decision-making process. The various objectives on both sides of engagement can make the experience challenging; there are no clear metrics for success. The situation is challenging because public input occurs within the context of the local legislative framework, regulatory requirements, and the peculiarities of the fairly recent biosafety frameworks, as well as of public opinion and individual values. Public engagement may be conducted voluntarily, or may be driven by legislation. What can be taken into account by the decision makers, and therefore what will be gathered and the timing of consultation, also may be legally defined. Several practical experiences suggest practices for effective engagement within the confines of regulatory mandates: (1) utilizing a range of resources to facilitate public education and opportunities for understanding complex technologies; (2) defining in advance the goal of seeking input; (3) identifying and communicating with the critical public groups from which input is needed; (4) using a clearly defined approach to gathering and assessing what will be used in making the biosafety decision; and (5) communicating using clear and simple language. These practices create a foundation for systematic methods to gather, acknowledge, respond to, and even incorporate public input. Applying such best practices will increase transparency and optimize the value of input from the public.

Influence of experimental conditions on osteoblast activity in human primary bone cell cultures.

Primary bone cell cultures were derived from human bone explants. Cellular activity was characterized by the alkaline phosphatase (AP) activity, osteocalcin, and type I and III collagen secretions in the supernatant. The determination of bone cell activity was performed in three different wells. No significant difference was noted between wells: the coefficient of variation was 8.0 +/- 2.9% for AP activity, 18.3 +/- 1.9% for osteocalcin secretion, and 22.5 +/- 14.3% for collagen. The AP activity and osteocalcin secretion significantly decreased with the number of passages: they were the highest after the first passage. Between each subject, the coefficient of variation was 85% for AP activity and osteocalcin secretion and 63 and 57% for type I and III collagen secretion, respectively. The AP activity did not differ with the age or sex of the donor. In contrast, osteocalcin secretion was significantly lower in females than in males. In males, osteocalcin significantly decreased with the age of the donor (r = -0.61; p less than 0.05). Cellular activity did not depend on the site of the biopsy. When bone explants from one donor were cultured in two different petri dishes, the activity of cells was similar in both dishes, except in one case. Primary cell cultures derived from human bone explants are the only model providing untransformed osteoblastlike cells of human origin. Because of the experimental conditions, some factors may have influenced the cellular activity and they must be taken into account to validate further in vitro studies.

Diurnal rhythm of axillary temperature in long and short sleepers: effects of sleep deprivation and sleep displacement.

Six habitual long (greater than or equal to 9 hr) sleepers (LS) and 6 habitual short (less than or equal to 6.5 hr) sleepers (SS) measured their diurnal axillary temperature (T) every 4 hr from awakening time to bedtime. For the control span of 10 days, temperature peak time was similar in both groups but occurred later in SS than in LS when measured from midsleep. Bedtime was closer to temperature peak time in LS than in SS. While experiencing the same sleep deprivations (SD 24 hr with morning sleep recovery and SD 36 hr with nocturnal sleep recovery). SS maintained a more stable body temperature curve than LS. After the nights of sleep deprivation, morning temperature increased in LS but not in SS. In both experimental conditions LS tended to advance their temperature peaks. This shift resulted in a statistically significant difference between the groups' T peaks for the 36-hour sleep deprivation. These results suggest that coupling between sleep/activity rhythm and temperature rhythm probably is different in LS and in SS, being stronger in LS.

Genome-wide survey of SNP variation uncovers the genetic structure of cattle breeds.

The imprints of domestication and breed development on the genomes of livestock likely differ from those of companion animals. A deep draft sequence assembly of shotgun reads from a single Hereford female and comparative sequences sampled from six additional breeds were used to develop probes to interrogate 37,470 single-nucleotide polymorphisms (SNPs) in 497 cattle from 19 geographically and biologically diverse breeds. These data show that cattle have undergone a rapid recent decrease in effective population size from a very large ancestral population, possibly due to bottlenecks associated with domestication, selection, and breed formation. Domestication and artificial selection appear to have left detectable signatures of selection within the cattle genome, yet the current levels of diversity within breeds are at least as great as exists within humans.

[Spontaneous spinal epidural haematoma during pregnancy]. / Hématome péridural rachidien spontané au cours de la grossesse.

Spontaneous spinal epidural haematomas are quite rare. We report here the case of a 27-year-old woman, without previous history of relevant medical disorder, who presented with acute paraplegia at 36 weeks of gestation. MRI performed in emergency revealed a T8 epidural haematoma. The management consisted in an emergency Caesarean section under general anaesthesia, followed immediately by a T8 laminectomy allowing the spinal cord decompression 14 hours after the first symptoms. Neurologic recovery was rapid and complete, except for bladder dysfunction persisting one month later. Spontaneous spinal epidural haematomas require a prompt diagnosis because neurologic prognosis essentially depends on the interval of time between onset of symptoms and surgical decompression. Obstetrical management especially depends on the term of pregnancy. For the anaesthesiologist, the difficulty is the management of both pregnant condition (full stomach general anaesthesia) and spinal cord compression (maintenance of spinal cord perfusion pression and limitation of ischaemia and oedema).

Expression of Semaphorin-3A and its receptors in endochondral ossification: potential role in skeletal development and innervation.

Bone tissue is densely innervated, and there is increasing evidence for a neural control of bone metabolism. Semaphorin-3A is a very important regulator of neuronal targeting in the peripheral nervous system as well as in angiogenesis, and knockout of the Semaphorin-3A gene induces abnormal bone and cartilage development. We analyzed the spatial and temporal expression patterns of Semaphorin-3A signaling molecules during endochondral ossification, in parallel with the establishment of innervation. We show that osteoblasts and chondrocytes differentiated in vitro express most members of the Semaphorin-3A signaling system (Semaphorin-3A, Neuropilin-1, and Plexins-A1 and -A2). In vitro, osteoclasts express most receptor chains but not the ligand. In situ, these molecules are all expressed in the periosteum and by resting, prehypertrophic and hypertrophic chondrocytes in ossification centers before the onset of neurovascular invasion. They are detected later in osteoblasts and also osteoclasts, with differences in intensity and regional distribution. Semaphorin-3A and Neuropilin-1 are also expressed in the bone marrow. Plexin-A3 is not expressed by bone cell lineages in vitro. It is detected early in the periosteum and hypertrophic chondrocytes. After the onset of ossification, this chain is restricted to a network of cell processes in close vicinity to the cells lining the trabeculae, similar to the pattern observed for neural markers at the same stages. After birth, while the density of innervation decreases, Plexin-A3 is strongly expressed by blood vessels on the ossification front. In conclusion, Semaphorin-3A signaling is present in bone and seems to precede or coincide at the temporal but also spatial level with the invasion of bone by blood vessels and nerve fibers. Expression patterns suggest Plexin-A3/Neuropilin-1 as a candidate receptor in target cells for the regulation of bone innervation by Semaphorin-3A.

Normal carboxylation of circulating osteocalcin (bone Gla-protein) in Paget's disease of bone.

Serum osteocalcin (bone Gla-protein), a specific marker of osteoblastic activity, is only moderately increased in patients with active Paget's disease of bone, despite biochemical evidence of increased bone turnover. Because pagetic bone has an abnormal texture, such a discrepancy could be due to an abnormal carboxylation of osteocalcin. To test this hypothesis, we measured the fraction of decarboxylated osteocalcin in the serum of 11 patients with active Paget's disease of bone by the hydroxyapatite binding technique and the data were compared to those obtained in 10 controls and in 10 patients on vitamin K antagonist therapy. In contrast to the decreased decarboxylated fraction of osteocalcin in warfarin-treated patients (27 +/- 2.2%, P less than 0.01 vs controls), the fraction of decarboxylated osteocalcin was normal in pagetic patients (8.9 +/- 2.2% vs 6.5 +/- 1.7% in controls, n.s.). These data suggest that there is no abnormality of the osteocalcin carboxylation in Paget's disease. The disproportionate levels of circulating osteocalcin compared to the marked elevation of alkaline phosphatase in that disease could be due to other factors such as an increased binding of the protein to the woven bone matrix.

Decorin inhibits cell migration through a process requiring its glycosaminoglycan side chain.

Several studies overwhelmingly support the notion that decorin (DCN) is involved in matrix assembly, and in the control of cell adhesion and proliferation. However, nothing is known about the role of DCN during cell migration. Cell migration is a tightly regulated process which requires both adhesion (at the leading edge of the cell) and de-adhesion (at the trailing edge of the cell) from the substratum. We have determined in this study the effect of DCN on MG-63 osteosarcoma cell migration and have analyzed whether its effect is mediated by the protein core and/or the glycosaminoglycan side chain. DCN impeded the migration-promoting effect of matrix molecules (fibronectin, collagen type I) known to interact with the proteoglycan. Conversely, DCN did not counteract the migration-promoting effect of fibrinogen lacking proteoglycan affinity. DCN bearing dermatan-sulfate chains (i.e., skin and cartilage DCN) was about 20-fold more effective in inhibiting cell migration than DCN bearing chondroitin-sulfate chains (i.e., bone DCN). In addition, chondroitinase AC-treatment of cartilage DCN (which specifically removes chondroitin-sulfate chains) did not attenuate the inhibitory effect of this proteoglycan, while cartilage DCN deprived of both chondroitin- and dermatan-sulfate chains failed to alter cell migration promoted by either fibronectin or its heparin- and cell-binding domains. These data assert that the dermatan-sulfate chains of DCN are responsible for a negative influence on cell migration. However, isolated glycosaminoglycans failed to alter cell migration promoted by fibronectin, indicating that strongly negatively charged glycosaminoglycans alone cannot account for the impaired cell motility seen with DCN. Overall, these results show that the inhibitory action of DCN is dependent of substratum binding, is differentially mediated by its glycosaminoglycan side chains (chondroitin-sulfate vs. dermatan-sulfate chains), and is independent of a steric hindrance effect exerted by its glycosaminoglycan side chains.