TGFB3
Transforming growth factor beta-3 proprotein precursor [Contains: Latency-associated peptide (LAP); Transforming growth factor beta-3 (TGF-beta-3)]
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Nowadays, paracrine regulation is considered as a major tool of mesenchymal stem cell (MSC) involvement in tissue repair and renewal in adults. Aging results in alteration of tissue homeostasis including neovascularization. In this study, we examined the influence of replicative senescence on the angiogenic potential of adipose-derived MSCs (ASCs). Angiogenic activity of conditioned medium (CM) from senescent and "young" ASCs was evaluated in chorioallantoic membrane (CAM) assay in ovo using Japanese quail embryos. Also, the formation of capillary-like tubes by human umbilical vein endothelial cells (HUVECs) in 3D basement membrane matrix Matrigel and HUVEC migration capacity were analyzed. Multiplex, dot-blot and gene expression analysis were performed to characterize transcription and production of about 100 angiogenesis-associated proteins. The results point to decreased angiogenic potential of senescent ASC secretome in ovo. A number of angiogenesis-associated proteins demonstrated elevation in CM after long-term cultivation. Meanwhile, VEGF (key positive regulator of angiogenesis) did not change transcription level and concentration in CM. Increasing both pro- (FGF-2, uPA, IL-6, IL-8 etc.) and antiangiogenic (IL-4, IP-10, PF4, Activin A, DPPIV etc.) factors was observed. Some proangiogenic genes were downregulated ([i]IGF1, MMP1, TGFB3, PDGFRB, PGF[/i]). Senescence-associated secretory phenotype (SASP) modifications after long-term cultivation lead to attenuation of angiogenic potential of ASC.
MeSH Terms
- Adult
- Angiogenic Proteins
- Cell Movement
- Cell Proliferation
- Cells, Cultured
- Cellular Senescence
- Chorioallantoic Membrane
- Female
- Human Umbilical Vein Endothelial Cells
- Humans
- Mesenchymal Stem Cells
- Middle Aged
- Neovascularization, Physiologic
- Paracrine Communication
Keywords
- adipose-derived mesenchymal stem cells (ASCs)
- angiogenesis
- replicative senescence
- senescence-associated secretory phenotype (SASP)
Do seminal plasma transforming growth factor-β (TGFB) cytokines vary within individuals over time, and does this relate to sperm parameters, age or prior abstinence? Activin A and follistatin, and to a lesser extent TGFB1, TGFB2 and TGFB3, vary within individuals over time, in association with duration of abstinence. Seminal plasma TGFB cytokines can influence sperm function and reproductive success through interactions with the female reproductive tract after coitus. Over time, individual sperm parameters fluctuate considerably. Whether seminal fluid TGFB cytokines vary similarly, and the determinants of any variance, is unknown. Between two and seven semen samples were collected from each of 14 fertile donors at 6-10 week intervals over the course of 12 months, then seminal plasma cytokines and sperm parameters were measured. The concentrations and total amounts per ejaculate of TGFB1, TGFB2, TGFB3, activin A and follistatin were determined using commercial assays. Sperm parameters were assessed according to WHO IV standards. Mixed model analysis was utilised to determine the relative contribution of between- and within-individual factors to the variance. Relationships between cytokines and sperm parameters, as well as effect of age and duration of abstinence, were investigated by correlation analysis. Within-individual variability contributed to the total variance for all cytokines and sperm parameters, and was a stronger determinant than between-individual variability for activin A and follistatin as well as for total sperm concentration and sperm motility. Positive correlations between each of the three TGFB isoforms, and activin and follistatin, suggest co-regulation of synthesis. Duration of abstinence influenced total content of TGFB1, TGFB2, activin A and follistatin. TGFB1 correlated inversely with age. A limited number of donors from a single clinic were investigated. Clinical information on BMI, nutrition, smoking and other lifestyle factors was unavailable. Further studies are required to determine whether the findings can be generalised to larger populations and different ethnicities. These data reveal substantial variation over time in seminal fluid cytokines and indicate that repeated analyses are required to gain precise representative data on an individual's status. Within-individual variation in seminal fluid components should be taken into account when investigating seminal fluid cytokines. This study was supported by grants from the National Health and Medical Research Council of Australia, ID453556 and APP1041332. The authors have no competing interests to disclose.
MeSH Terms
- Activins
- Adolescent
- Adult
- Age Factors
- Aging
- Follistatin
- Humans
- Male
- Middle Aged
- Semen
- Semen Analysis
- Sperm Count
- Transforming Growth Factor beta
- Young Adult
Keywords
- cytokines
- fertility
- seminal plasma
- sperm
- variation
Articular cartilage undergoes substantial age-related changes in molecular composition, matrix structure, and mechanical properties. These age-related differences between juvenile and adult cartilage manifest themselves as markedly distinct potentials for tissue repair and regeneration. To compare the biological properties and tissue regeneration capabilities of juvenile and adult bovine articular cartilage. Controlled laboratory study. Articular cartilage harvested from juvenile (age, 4 months) and adult (age, 6-8 years) bovine femoral condyles was cultured for 4 weeks to monitor chondrocyte migration, glycosaminoglycan content conservation, and new tissue formation. The cartilage cell density and proliferative activity were also compared. Additionally, the effects of age-related changes on cartilage gene expression were analyzed using the Affymetrix GeneChip array. Compared with adult cartilage, juvenile bovine cartilage demonstrated a significantly greater cell density, higher cell proliferation rate, increased cell outgrowth, elevated glycosaminoglycan content, and enhanced matrix metallopeptidase 2 activity. During 4 weeks in culture, only juvenile cartilage was able to generate new cartilaginous tissues, which exhibited pronounced labeling for proteoglycan and type II collagen but not type I collagen. With over 19,000 genes analyzed, distinctive gene expression profiles were identified. The genes mostly involved in cartilage growth and expansion, such as COL2A1, COL9A1, MMP2, MMP14, and TGFB3, were upregulated in juvenile cartilage, whereas the genes primarily responsible for structural integrity, such as COMP, FN1, TIMP2, TIMP3, and BMP2, were upregulated in adult cartilage. As the first comprehensive comparison between juvenile and adult bovine articular cartilage at the tissue, cellular, and molecular levels, the results strongly suggest that juvenile cartilage possesses superior chondrogenic activity and enhanced regenerative potential over its adult counterpart. Additionally, the differential gene expression profiles of juvenile and adult cartilage suggest possible mechanisms underlying cartilage age-related changes in their regeneration capabilities, structural components, and biological properties. The results of this comparative study between juvenile and adult bovine articular cartilage suggest an enhanced regenerative potential of juvenile cartilage tissue in the restoration of damaged articular cartilage.
MeSH Terms
- Aging
- Animals
- Cartilage, Articular
- Cattle
- Cell Count
- Cell Proliferation
- Chondrocytes
- Gene Expression Profiling
- Glycosaminoglycans
- Matrix Metalloproteinase 2
- Oligonucleotide Array Sequence Analysis
- Regeneration
Keywords
- adult
- aging
- articular cartilage
- biology of cartilage
- bovine
- cartilage regeneration
- cartilage repair
- chondrocyte
- gene expression
- juvenile
- knee
- migration