Prediction of Preterm Delivery Using Serum Ischemia Modified Albumin, Biglycan, and Decorin Levels in Women with Threatened Preterm Labor.

OBJECTIVE: The serum ischemia modified albumin (IMA), biglycan, and decorin levels of pregnant women who were hospitalized for threatened preterm labor were measured. METHODS: Fifty-one consecutive pregnant women with a single pregnancy between the 24th and 36th weeks with a diagnosis of threatened preterm labor were included in the present prospective cohort study. RESULTS: As a result of multivariate logistic regression analysis for predicting preterm delivery within 24 hours, 48 hours, 7 days, 14 days, ≤ 35 gestational weeks, and ≤ 37 gestational weeks after admission, area under the curve (AUC) (95% confidence interval [CI[) values were 0.95 (0.89-1.00), 0.93 (0.86-0.99), 0.91 (0.83-0.98), 0.92 (0.85-0.99), 0.82 (0.69-0.96), and 0.89 (0.80-0.98), respectively. In the present study, IMA and biglycan levels were found to be higher and decorin levels lower in women admitted to the hospital with threatened preterm labor and who gave preterm birth within 48 hours compared with those who gave birth after 48 hours. CONCLUSION: In pregnant women admitted to the hospital with threatened preterm labor, the prediction preterm delivery of the combined model created by adding IMA, decorin, and biglycan in addition to the TVS CL measurement was higher than the TVS CL measurement alone. CLINICAL TRIAL REGISTRATION: The present trial was registered at ClinicalTrials.gov, number NCT04451928.

OBJETIVO: Medir os níveis séricos de albumina modificada por isquemia (IMA), biglicano e decorina de gestantes hospitalizadas por ameaça de parto prematuro. MéTODOS: Cinquenta e uma mulheres grávidas consecutivas com uma única gravidez entre a 24ª e a 36ª semanas com diagnóstico de ameaça de trabalho de parto prematuro foram incluídas no presente estudo de corte prospectivo. RESULTADOS: Como resultado da análise de regressão logística multivariada para prever parto prematuro dentro de 24 horas, 48 horas, 7 dias, 14 dias, ≤ 35 semanas gestacionais e ≤ 37 semanas gestacionais após a admissão, área sob a curva (AUC) (95% de confiança os valores de intervalo [CI[) foram 0,95 (0,89­1,00), 0,93 (0,86­0,99), 0,91 (0,83­0,98), 0,92 (0,85­0,99), 0,82 (0,69­0,96) e 0,89 (0,80­0,98), respectivamente. No presente estudo, os níveis de IMA e biglican foram maiores e os níveis de decorin menores em mulheres admitidas no hospital com ameaça de trabalho de parto prematuro e que tiveram parto prematuro em 48 horas em comparação com aquelas que deram à luz após 48 horas. CONCLUSãO: Em gestantes admitidas no hospital com ameaça de trabalho de parto prematuro, a predição de parto prematuro do modelo combinado criado pela adição de IMA, decorin e biglican, além da medição do TVS CL, foi maior do que a medição do TVS CL isoladamente. REGISTRO DO ENSAIO CLíNICO: O presente ensaio foi registrado em ClinicalTrials.gov, número NCT04451928.

Deep learning neural network image analysis of immunohistochemical protein expression reveals a significantly reduced expression of biglycan in breast cancer.

New breast cancer biomarkers have been sought for better tumor characterization and treatment. Among these putative markers, there is Biglycan (BGN). BGN is a class I small leucine-rich proteoglycan family of proteins characterized by a protein core with leucine-rich repeats. The objective of this study is to compare the protein expression of BGN in breast tissue with and without cancer, using immunohistochemical technique associated with digital histological score (D-HScore) and supervised deep learning neural networks (SDLNN). In this case-control study, 24 formalin-fixed, paraffin-embedded tissues were obtained for analysis. Normal (n = 9) and cancerous (n = 15) tissue sections were analyzed by immunohistochemistry using BGN monoclonal antibody (M01-Abnova) and 3,3'-Diaminobenzidine (DAB) as the chromogen. Photomicrographs of the slides were analysed with D-HScore, using arbitrary DAB units. Another set (n = 129) with higher magnification without ROI selection, was submitted to the inceptionV3 deep neural network image embedding recognition model. Next, supervised neural network analysis, using stratified 20 fold cross validation, with 200 hidden layers, ReLu activation, and regularization at α = 0.0001 were applied for SDLNN. The sample size was calculated for a minimum of 7 cases and 7 controls, having a power = 90%, an α error = 5%, and a standard deviation of 20, to identify a decrease from the average of 40 DAB units (control) to 4 DAB units in cancer. BGN expression in DAB units [median (range)] was 6.2 (0.8 to 12.4) and 27.31 (5.3 to 81.7) in cancer and normal breast tissue, respectively, using D-HScore (p = 0.0017, Mann-Whitney test). SDLNN classification accuracy was 85.3% (110 out of 129; 95%CI = 78.1% to 90.3%). BGN protein expression is reduced in breast cancer tissue, compared to normal tissue.

Expression of proteoglycans in two types of ameloblastoma: novel Immunohistochemical findings.

Alterations in cellular and extracellular matrix components play an important role during tumorigenesis; proteoglycans are included among these components. Ameloblastomas are odontogenic tumors distinguished as invasive and infiltrative neoplasms and are divided into different histological types, the most common of which are the unicystic ameloblastoma and the conventional ameloblastoma. The aim of this study was to identify the presence of two proteoglycans, perlecan and biglycan, in different types of ameloblastoma. Using immunohistochemistry, we determined the presence of both proteins in 28 unicystic ameloblastomas and 23 conventional ameloblastomas. We identified the cytoplasmic and nuclear presence of perlecan and the cytoplasmic presence of biglycan in both types of ameloblastoma. The mean values of immunoexpression were higher in the conventional type compared to the unicystic type. Neither the presence of biglycan in ameloblastomas nor the nuclear presence of perlecan in any odontogenic tumor has previously been reported. The differential immunoexpression of perlecan and biglycan in these types of ameloblastomas suggests their participation in the developmental process of these tumors.

Decorin and biglycan immunolocalization in non-villous structures of healthy and pathological human placentas.

AIMS: Decorin and biglycan are members of the small leucine-rich proteoglycan family, and constituents of both the extracellular matrix (ECM) and the cell surface. They are recognized as important factors in the control of proliferation, migration and invasion in vivo and in vitro. In this study, the localization patterns of decorin and biglycan were determined in healthy placentas and in highly invasive placental pathologies. METHODS AND RESULTS: The study included immunolocalization of decorin and biglycan in samples of first-trimester and term placentas, placenta accreta, invasive mole, and choriocarcinoma. Extravillous cytotrophoblast (EVT) cells were positive for both proteoglycans in all pathologies and in first-trimester placentas, although not in term placentas. Biglycan was immunolocalized in the ECM of all healthy and pathological placentas, whereas decorin was observed only in term placenta ECM. CONCLUSIONS: The expression of both proteoglycans was cell-specific and gestation time-dependent in healthy placentas, and was associated with invasive EVT cells in pathological placentas. In view of the biological properties of these molecules, it is possible that the biglycan pattern found here is intrinsically implicated in the invasive activity of EVT cells in both healthy and disordered placentas.

Immunohistochemical expression of biglycan and decorin in the pulp tissue of human primary teeth during resorption.

Primary teeth are interesting models that can be used to study physiological and pathological processes involving cells and extracellular matrices in hard and soft tissues. This study investigated the expression and distribution of biglycan and decorin-the non-collagenous components of the extracellular matrix-in primary teeth tissue, during physiological root resorption. Thirty healthy human primary teeth were grouped together according to root length: Group I - two-thirds root length, Group II - one-third root length, and Group III - teeth with no root. The streptavidin-biotin-peroxidase immunohistochemical method was used with antibodies against the previously named antigens. The proteoglycans studied were found in the pulp and dentin extracellular matrix in all groups without any differences in the proteins, among the groups. Biglycan was observed mainly in predentin and in pulp connective tissue in the resorption area. In addition, decorin was observed mainly in pulp connective tissue, but near the resorption area. Biglycan and decorin were distributed differentially in the dental tissues. The present immunohistocytochemical data, combined with previously reported data, suggest that these proteoglycans could be involved in regulating the physiological resorption process in healthy primary teeth.

Immunohistochemical expression of biglycan and decorin in the pulp tissue of human primary teeth during resorption

Primary teeth are interesting models that can be used to study physiological and pathological processes involving cells and extracellular matrices in hard and soft tissues. This study investigated the expression and distribution of biglycan and decorin-the non-collagenous components of the extracellular matrix-in primary teeth tissue, during physiological root resorption. Thirty healthy human primary teeth were grouped together according to root length: Group I - two-thirds root length, Group II - one-third root length, and Group III - teeth with no root. The streptavidin-biotin-peroxidase immunohistochemical method was used with antibodies against the previously named antigens. The proteoglycans studied were found in the pulp and dentin extracellular matrix in all groups without any differences in the proteins, among the groups. Biglycan was observed mainly in predentin and in pulp connective tissue in the resorption area. In addition, decorin was observed mainly in pulp connective tissue, but near the resorption area. Biglycan and decorin were distributed differentially in the dental tissues. The present immunohistocytochemical data, combined with previously reported data, suggest that these proteoglycans could be involved in regulating the physiological resorption process in healthy primary teeth.

Evaluation of the effects of transient or continuous PTH administration to odontoblast-like cells.

Parathyroid hormone participates in the metabolism of mineralized tissue. Its role in the formation of dentine is, as yet, incompletely understood. In the present study we analyzed the effect of transient (1 and 24-h/cycle) or continuous hPTH (1-34) treatment in odontoblast-like cells (MDPC-23) to the following parameters: mineral deposition detected by alizarin red, mRNA expression of the type I collagen (COL1), alkaline phosphatase (ALP), biglycan (BGN), matrix metalloproteinase 2 (MMP-2) and dentine sialophosphoprotein (DSPP) quantified by qRT-PCR. MMP-2 and ALP activities were quantified by zymography and colorimetric assay, respectively. The results showed that compared to Control group: intermittent PTH administration (1 and 24-h/cycle) decreased the mineral deposition and ALP activity. DSPP gene expression was not detected in both control and PTH treated cells. The PTH administration for 24-h/cycle increased the ALP, BGN and COL1 mRNA expression and continuous PTH treatment increased BGN and COL1 mRNA expression. Zymography assays showed that compared to Control group: PTH treatment for 1-h/cycle increased the total MMP-2 secretion and the continuous treatment decreased the secreted levels of MMP-2 active-form. Taken together, the results shown that PTH may regulate the odontoblast-like cells-induced secretion, and potentially this hormone can affect in vivo odontoblasts functions.

Extracellular matrix composition in COPD.

Extracellular matrix (ECM) composition has an important role in determining airway structure. We postulated that ECM lung composition of chronic obstructive pulmonary disease (COPD) patients differs from that observed in smoking and nonsmoking subjects without airflow obstruction. We determined the fractional areas of elastic fibres, type-I, -III and -IV collagen, versican, decorin, biglycan, lumican, fibronectin and tenascin in different compartments of the large and small airways and lung parenchyma in 26 COPD patients, 26 smokers without COPD and 16 nonsmoking control subjects. The fractional area of elastic fibres was higher in non-obstructed smokers than in COPD and nonsmoking controls, in all lung compartments. Type-I collagen fractional area was lower in the large and small airways of COPD patients and in the small airways of non-obstructed smokers than in nonsmokers. Compared with nonsmokers, COPD patients had lower versican fractional area in the parenchyma, higher fibronectin fractional area in small airways and higher tenascin fractional area in large and small airways compartments. In COPD patients, significant correlations were found between elastic fibres and fibronectin and lung function parameters. Alterations of the major ECM components are widespread in all lung compartments of patients with COPD and may contribute to persistent airflow obstruction.

Gene expression analysis of demineralized bone matrix-induced osteogenesis in human periosteal cells using cDNA array technology.

Demineralized bone matrix (DBM) has been widely investigated as a biomaterial to promote new bone formation and is utilized clinically for bone repair and regeneration. We investigated gene expression patterns of osteogenic differentiation in human periosteal (HPO) cells cultured with demineralized bone matrix, using cDNA array technology. Osteogenic differentiation of HPO cells was determined using alkaline phosphatase assay. In order to examine differential gene expression during osteogenic differentiation, total RNA was isolated from HPO cells in the absence or presence of DBM on day seven and analyzed using osteogenesis cDNA gene array. The selected genes were verified using reverse transcriptase (RT)-PCR analysis. Human periosteal cells differentiated along an osteogenic lineage after treatment of DBM. The alkaline phosphatase activity assay showed that HPO cells differentiated into an osteogenic lineage. Gene expression of HPO cells treated with DBM for seven days was analyzed with cDNA array and RT-PCR analyses. Expression of biglycan, TGF-ß1, and TGF-ßR1 was upregulated, whereas collagen14A1 expression was downregulated, as confirmed by RT-PCR. Human periosteal cells expressed osteogenesis genes when treated with DBM. These findings provide new insight into the capability of demineralized bone matrix to modulate the osteogenic differentiation of human periosteal cells.

Decorin and biglycan expression: its relation with endothelial heterogeneity.

Decorin and biglycan proteoglycans play important roles in the organization of the extracellular matrix, and in the regulation of cell adhesion and migration. Given morphological and functional endothelial heterogeneity, information is needed regarding whether endothelial cells (ECs) from different vascular beds possess different profiles of proteoglycan constituents of the basement membranes. Here, we report that endothelia from different murine organs and EC lines derived thereof produce and secrete different patterns of proteoglycans. A faint colocalization between decorin and PECAM/CD31 was found on tissue sections from mouse heart, lung and kidney by immunofluorescence. Three EC lines derived from these organs produced decorin (100-kDa) and its core protein (45-kDa). Extracellular decorin recognition in culture supernatant was only possible after chondroitin lyase digestion suggesting that the core protein of secreted proteoglycan is more encrypted by glycosaminoglycans than the intracellular one. Heart and lung ECs were able to produce and release decorin. Kidney ECs synthesized the proteoglycan and its core protein but no secretion was detected in culture supernatants. Although biglycan production was recorded in all EC lines, secretion was almost undetectable, consistent with immunofluorescence results. In addition, no biglycan secretion was detected after EC growth supplement treatment, indicating that biglycan is synthesized, secreted and quickly degraded extracellularly by metalloproteinase-2. Low molecular-mass dermatan sulfate was the predominant glycosaminoglycan identified bound to the core protein. ECs from different vascular beds, with differences in morphology, physiology and cell biology show differences in the proteoglycan profile, extending their heterogeneity to potential differences in cell migration capacities.

Modulation of small leucine-rich proteoglycans (SLRPs) expression in the mouse uterus by estradiol and progesterone.

BACKGROUND: We have previously demonstrated that four members of the family of small leucine-rich-proteoglycans (SLRPs) of the extracellular matrix (ECM), named decorin, biglycan, lumican and fibromodulin, are deeply remodeled in mouse uterine tissues along the estrous cycle and early pregnancy. It is known that the combined action of estrogen (E2) and progesterone (P4) orchestrates the estrous cycle and prepares the endometrium for pregnancy, modulating synthesis, deposition and degradation of various molecules. Indeed, we showed that versican, another proteoglycan of the ECM, is under hormonal control in the uterine tissues. METHODS: E2 and/or medroxiprogesterone acetate (MPA) were used to demonstrate, by real time PCR and immunoperoxidase staining, respectively, their effects on mRNA expression and protein deposition of these SLRPs, in the uterine tissues. RESULTS: Decorin and lumican were constitutively expressed and deposited in the ECM in the absence of the ovarian hormones, whereas deposition of biglycan and fibromodulin were abolished from the uterine ECM in the non-treated group. Interestingly, ovariectomy promoted an increase in decorin, lumican and fibromodulin mRNA levels, while biglycan mRNA conspicuously decreased. Hormone replacement with E2 and/or MPA differentially modulates their expression and deposition. CONCLUSIONS: The patterns of expression of these SLRPs in the uterine tissues were found to be hormone-dependent and uterine compartment-related. These results reinforce the existence of subpopulations of endometrial fibroblasts, localized into distinct functional uterine compartments, resembling the organization into basal and functional layers of the human endometrium.

Collagen fibril organization in the pregnant endometrium of decorin-deficient mice.

In the pregnant mouse endometrium, collagen fibrillogenesis is characterized by the presence of very thick collagen fibrils which are topographically located exclusively within the decidualized stroma. This dynamic biological process is in part regulated by the small leucine-rich proteoglycans decorin and biglycan. In the present study we utilized wild-type (Dcn(+/+)) and decorin-deficient (Dcn(-/-)) time-pregnant mice to investigate the evolution of non-decidualized and decidualized collagen matrix in the uterine wall of these animals. Ultrastructural and morphometric analyses revealed that the organization of collagen fibrils in the pregnant endometrium of both non-decidualized and decidualized stroma showed a great variability of shape and size, regardless of the genotype. However, the decidualized endometrium from Dcn(-/-) mice contained fibrils with larger diameter and more irregular contours as compared to the wild-type littermates. In the Dcn(-/-) animals, the proportion of thin (10-50 nm) fibrils was also higher as compared to Dcn(+/+) animals. On day 7 of pregnancy, biglycan was similarly localized in the decidualized endometrium in both genotypes. Lumican immunostaining was intense both in decidualized and non-decidualized stroma from Dcn(-/-) animals. The present results support previous findings suggesting that decorin participates in uterine collagen fibrillogenesis. In addition, we suggest that the absence of decorin disturbs the process of lateral assembly of thin fibrils, resulting in very thick collagen fibrils with irregular profiles. Our data further suggest that decorin, biglycan and lumican might play an interactive role in collagen fibrillogenesis in the mouse endometrium, a process modulated according to the stage of pregnancy.

Maternal diabetes affects specific extracellular matrix components during placentation.

During embryo implantation, invasive trophoblast cells mediate embryo invasion into the decidualized stroma, forming a rich network of lacunae that connect the embryonic tissues to the maternal blood vessels. Placentation is probably guided by the composition and organization of the endometrial extracellular matrix. Certain pathological conditions that occur during pregnancy, including diabetes, have been linked to abnormal placental morphology and consequent fetal morbidity. We used immunoperoxidase techniques to identify members of the collagen, proteoglycan and glycoprotein families in the various compartments of the rat placenta and to determine whether experimentally induced diabetes affects placental morphology and alters the distribution of these molecules during pregnancy. Single injections of alloxan (40 mg kg(-1) i.v.) were used to induce diabetes on day 2 of pregnancy in Wistar rats. Placentas were collected on days 14, 17, and 20. Type I and III collagen, as well as the proteoglycans decorin and biglycan, were found to be distributed throughout the placentas of control and diabetic rats. In both groups, laminin expression decreased at the end of pregnancy. In contrast, fibronectin was detected in the labyrinth region of diabetic rats at all gestational stages studied, whereas it was detected only at term pregnancy in the placentas of control rats. These results show for the first time that some extracellular matrix molecules are modulated during placental development. However, as diabetic rats presented increased fibronectin deposition exclusively in the labyrinth region, we speculate that diabetes alters the microenvironment at the maternal-fetal interface, leading to developmental abnormalities in the offspring.

Characterization and distribution of hyaluronan and the proteoglycans decorin, biglycan and perlecan in the developing embryonic mouse gonad.

The morphogenesis of tissues and organs requires dynamic changes in cells and in extracellular matrix components. It is known that various extracellular matrix molecules are of fundamental importance for gonad differentiation and growth. In the adult testis, the extracellular matrix represents an important component of the interstitium, participating in the transport of biologically active substances needed for the communication between different cellular components, as well as for the regulation of spermatogenesis and hormone production. The present study was designed in order to identify the proteoglycans biglycan, decorin and perlecan, as well as the glycosaminoglycan hyaluronan, during testis development in mouse embryos. Our data profile the chronology of testis differentiation, as well as the distribution of these extracellular matrix components during testis development in mice. We show that these extracellular matrix molecules are present early in the development of the gonads, suggesting that they play a role in gonad development. In addition, we found no decorin in the testicular cords. Furthermore, of the proteoglycans analysed, only biglycan was seen surrounding immature Sertoli cells and Leydig cell precursors in the testicular cords. This indicates that specific sets of extracellular matrix molecules are required in the various compartments of the developing gonad.

Increase in decorin and biglycan in Duchenne Muscular Dystrophy: role of fibroblasts as cell source of these proteoglycans in the disease.

Fibrosis is a common pathological feature observed in muscles of patients with Duchenne muscular dystrophy (DMD). Biglycan and decorin are small chondroitin/dermatan sulfate proteoglycans in the muscle extracellular matrix (ECM) that belong to the family of structurally related proteoglycans called small leucine-rich repeat proteins. Decorin is considered an anti-fibrotic agent, preventing the process by blocking TGF-beta activity. There is no information about their expression in DMD patients. We found an increased amount of both proteoglycans in the ECM of skeletal muscle biopsies obtained from DMD patients. Both biglycan and decorin were augmented in the perimysium of muscle tissue, but only decorin increased in the endomysium as seen by immunohistochemical analyses. Fibroblasts were isolated from explants obtained from muscle of DMD patients and the incorporation of radioactive sulfate showed an increased synthesis of both decorin and biglycan in cultured fibroblasts compared to controls. The size of decorin and biglycan synthesized by DMD and control fibroblasts seems to be similar in size and anion charge. These findings show that decorin and biglycan are increased in DMD skeletal muscle and suggest that fibroblasts would be, at least, one source for these proteoglycans likely playing a role in the muscle response to dystrophic cell damage.

Extracellular proteoglycans modify TGF-beta bio-availability attenuating its signaling during skeletal muscle differentiation.

The onset and progression of skeletal muscle regeneration are controlled by a complex set of interactions between muscle precursor cells and their environment. Satellite cells constitute the main source of muscle precursor cells for growth and repair. After skeletal muscle injury, cell-derived signals induce their re-entry into the cell cycle and their migration into the damaged zone, where they proliferate and differentiate into mature myofibers. The surrounding extracellular matrix (ECM) together with inhibitory growth factors, such as transforming growth factor-beta (TGF-beta), also likely play an important role in growth control and muscle differentiation. Decorin, biglycan and betaglycan are proteoglycans that bind TGF-beta during skeletal muscle differentiation. In this paper, we show that the binding of TGF-beta to the receptors TGF-betaRI and-betaRII diminished in a satellite cell-derived cell line during differentiation, in spite of an increase expression of both receptors. In contrast, during the differentiation of decorin-null myoblasts (Dcn null), which lack decorin expression, the binding of TGF-beta to TGF-betaRI and -betaRII increased concomitantly with receptors levels. Both the addition and re-expression of decorin, in these myoblasts, diminished the binding of TGF-beta to its transducing receptors. Similar results were obtained when biglycan was added or over-expressed in Dcn null myoblasts. The binding of TGF-beta to TGF-betaRIII, alternatively known as betaglycan, was also augmented in Dcn null myoblasts and diminished by decorin, biglycan and betaglycan. These results suggest that decorin, biglycan and betaglycan compete for the binding of TGF-beta to its transducing receptors. Transfection studies with the TGF-beta-dependent promoter of the plasminogen activator inhibitor-1, coupled with luciferase, revealed that the addition of each proteoglycan diminished TGF-beta-dependent activity, for both TGF-beta1 and -beta2. The modulation of TGF-beta signaling by ECM proteoglycans diminishing the bio-availability of TGF-beta for its transducing receptors appears to be a feasible mechanism for the attenuation of this inhibitory growth factor during skeletal muscle formation.

Biglycan is a new extracellular component of the Chordin-BMP4 signaling pathway.

The BMP4 signaling pathway plays key roles during early embryonic development and for maintenance of adult homeostasis. In the extracellular space, BMP4 activity is regulated by a group of interacting molecules including the BMP antagonist Chordin, the metalloproteinase Tolloid and Twisted gastrulation (Tsg). In this study, we identified Biglycan (Bgn), a member of the small leucine-rich proteoglycan family, as a new extracellular modulator of BMP4 signaling. Xenopus Bgn (xBgn) is expressed uniformly in the ectoderm and mesoderm and their derivatives during development. Microinjection of Bgn mRNA induced secondary axes, dorsalized the mesoderm and inhibited BMP4 activity in Xenopus embryos. Biochemical experiments showed that Bgn binds BMP4 and Chordin, interaction that increased binding of BMP4 to Chordin. Bgn was also able to improve the efficiency of Chordin-Tsg complexes to block BMP4 activity. Using antisense morpholinos, we demonstrated that Bgn required Chordin to induce double axes in Xenopus. This work unveiled a new function for Bgn, its ability to regulate BMP4 signaling through modulation of Chordin anti-BMP4 activity.

Transient up-regulation of biglycan during skeletal muscle regeneration: delayed fiber growth along with decorin increase in biglycan-deficient mice.

The onset and progression of skeletal muscle regeneration are controlled by a complex set of interactions between muscle precursor cells and their environment. Decorin is the main proteoglycan present in the extracellular matrix (ECM) of adult muscle while biglycan expression is lower, but both are increased in mdx mice dystrophic muscle. Both of these small leucine-rich proteoglycans (SLRPs) can bind other matrix proteins and to the three TGF-beta isoforms, acting as modulators of their biological activity. We evaluated biglycan and decorin expression in skeletal muscle during barium chloride-induced skeletal muscle regeneration in mice. A transient and dramatic up-regulation of biglycan was associated with newly formed myotubes, whereas decorin presented only minor variations. Studies both in vitro and in intact developing newborn mice showed that biglycan expression is initially high and then decreases during skeletal muscle differentiation and maturation. To further evaluate the role of biglycan during the regenerative process, skeletal muscle regeneration was studied in biglycan-null mice. Skeletal muscle maintains its regenerative capacity in the absence of biglycan, but a delay in regenerated fiber growth and a decreased expression of embryonic myosin were observed despite to normal expression of MyoD and myogenin. Transient up-regulation of decorin during muscle regeneration in these mice may possibly obscure further roles of SLRPs in this process.