TGF-β2 enhances nanoscale cortex stiffness via condensation of cytoskeleton-focal adhesion plaque.

Physical spatiotemporal characteristics of cellular cortex dominate cell functions and even determine cell fate. The cellular cortex is able to reorganize to a dynamic steady status with changed stiffnesses once stimulated, and thus alter the physiological and pathological activities of almost all types of cells. TGF-β2, a potent pleiotropic growth factor, plays important roles in cartilage development, endochondral ossification, and cartilage diseases.

Runx1 alleviates osteoarthritis progression in aging mice.

With rates growing quickly with age, osteoarthritis (OA) is the most common cause of chronic disability in aging persons. The discomfort and reduced motion associated with osteoarthritis have a significant impact on quality of life, and there is no known solution. Runt-related transcription factor 1(Runx1) has been shown to play a protective role in the development of osteoarthritis by promoting chondrogenesis.

Biomimetic Fibers Based on Equidistant Micropillar Arrays Determines Chondrocyte Fate via Mechanoadaptability.

It is recognized that the changes in the physical properties of extracellular matrix (ECM) result in fine-tuned cell responses including cell morphology, proliferation and differentiation. In this study, a novel patterned equidistant micropillar substrate based on polydimethylsiloxane (PDMS) is designed to mimic the collagen fiber-like network of the cartilage matrix. By changing the component of the curing agent to an oligomeric base, micropillar substrates with the same topology but different stiffnesses are obtained and it is found that chondrocytes seeded onto the soft micropillar substrate maintain their phenotype by gathering type II collagen and aggrecan more effectively than those seeded onto the stiff micropillar substrate.

FGF19 induces the cell cycle arrest at G2-phase in chondrocytes.

Fibroblast growth factor 19 (FGF19) has appeared as a new possible avenue in the treatment of skeletal metabolic disorders. However, the role of FGF19 on cell cycle progression in skeletal system is poorly understood. Here we demonstrated that FGF19 had the ability to reduce the proliferation of chondrocytes and cause cell cycle G2 phase arrest through its interaction with β-Klotho (KLB), an important accessory protein that helps FGF19 link to its receptor.

Stiffened fibre-like microenvironment based on patterned equidistant micropillars directs chondrocyte hypertrophy.

Articular cartilage, composed of collagen type II as a major extracellular matrix and chondrocyte as a unique cell type, is a specialized connective tissue without blood vessels, lymphatic vessels and nerves. This distinctive characteristic of articular cartilage determines its very limited ability to repair when damaged. It is well known that physical microenvironmental signals regulate many cell behaviors such as cell morphology, adhesion, proliferation and cell communication even determine chondrocyte fate.

The role of fibroblast growth factor 7 in cartilage development and diseases.

Fibroblast growth factor 7 (FGF7), also known as keratinocyte growth factor (KGF), shows a crucial biological significance in tissue development, wound repair, tumorigenesis, and immune reconstruction. In the skeletal system, FGF7 directs the cellular synaptic extension of individual cells and facilities functional gap junction intercellular communication of a collective of cells. Moreover, it promotes the osteogenic differentiation of stem cells via a cytoplasmic signaling network.

FGF19 increases mitochondrial biogenesis and fusion in chondrocytes via the AMPKα-p38/MAPK pathway.

Fibroblast growth factor 19 (FGF19) is recognized to play an essential role in cartilage development and physiology, and has emerged as a potential therapeutic target for skeletal metabolic diseases. However, FGF19-mediated cellular behavior in chondrocytes remains a big challenge. In the current study, we aimed to investigate the role of FGF19 on chondrocytes by characterizing mitochondrial biogenesis and fission-fusion dynamic equilibrium and exploring the underlying mechanism.

IL-10 enhances cell-to-cell communication in chondrocytes via STAT3 signaling pathway.

Gap junction intercellular communication (GJIC) allows the transfer of material, message and energy between cells, which influences cell behaviors including cell proliferation, migration, differentiation and apoptosis and determines cell fate. Interleukin-10 (IL-10), a versatile cytokine, attracts more and more attention in the cartilage pathology such as osteoarthritis (OA) due to its potential in anti-inflammation and wound repair. However, whether IL-10 can mediate GJIC in chondrocytes remains elusive.

The roles of Runx1 in skeletal development and osteoarthritis: A concise review.

Runt-related transcription factor-1 (Runx1) is well known for its functions in hematopoiesis and leukemia but recent research has focused on its role in skeletal development and osteoarthritis (OA). Deficiency of the Runx1 gene is fatal in early embryonic development, and specific knockout of Runx1 in cell lineages of cartilage and bone leads to delayed cartilage formation and impaired bone calcification. Runx1 can regulate genes including collagen type II (Col2a1) and X (Col10a1), SRY-box transcription factor 9 (Sox9), aggrecan (Acan) and matrix metalloproteinase 13 (MMP-13), and the up-regulation of Runx1 improves the homeostasis of the whole joint, even in the pathological state.

TGF-β3 enhances cell-to-cell communication in chondrocytes via the ALK5/p-Smad3 axis.

Gap junctional intercellular communication (GJIC) is indispensable for the maintenance of physiological balance in articular cartilage. Transforming growth factor-β3 (TGF-β3), an important growth factor of TGF-β superfamily, is well recognized to play a unique regulatory role in cartilage development and diseases. However, the role of TGF-β3 in GJIC in adult chondrocytes remains elusive.

PTHrP promotes subchondral bone formation in TMJ-OA.

PTH-related peptide (PTHrP) improves the bone marrow micro-environment to activate the bone-remodelling, but the coordinated regulation of PTHrP and transforming growth factor-β (TGFβ) signalling in TMJ-OA remains incompletely understood. We used disordered occlusion to establish model animals that recapitulate the ordinary clinical aetiology of TMJ-OA. Immunohistochemical and histological analyses revealed condylar fibrocartilage degeneration in model animals following disordered occlusion.

Mammalian Sirtuins and Their Relevance in Vascular Calcification.

Cardiovascular diseases are a group of diseases with high morbidity and mortality that affect millions of people each year. Vascular calcification (VC) is an active process that involves the mineral deposition of calcium-phosphate complexes. VC is closely related to cardiovascular diseases, such as hypertension, heart failure, and calcific aortic stenosis, and is a type of ectopic calcification that occurs in the vessel walls.

Gold standard for nutrition: a review of human milk oligosaccharide and its effects on infant gut microbiota.

Human milk is the gold standard for nutrition of infant growth, whose nutritional value is mainly attributed to human milk oligosaccharides (HMOs). HMOs, the third most abundant component of human milk after lactose and lipids, are complex sugars with unique structural diversity which are indigestible by the infant. Acting as prebiotics, multiple beneficial functions of HMO are believed to be exerted through interactions with the gut microbiota either directly or indirectly, such as supporting beneficial bacteria growth, anti-pathogenic effects, and modulation of intestinal epithelial cell response.

The alteration of A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) in the knee joints of osteoarthritis mice.

The A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) family is gradually being recognized as an important family of mediators that, along with the matrix metalloproteinases (MMPs), control the degradation process in osteoarthritis (OA). The objective of this study was to uncover the detailed alterations of ADAMTS1, ADAMTS2, and ADAMTS5 in the knee joint of OA mice. The OA model was established by anterior cruciate ligament transection (ACLT) on the knee joints of C57BL/6 J mice.

Biomaterial Stiffness Guides Cross-talk between Chondrocytes: Implications for a Novel Cellular Response in Cartilage Tissue Engineering.

The exquisite cartilage architecture maintains an orderly dynamic equilibrium as a result of the interplay between chondrocyte functions and the unique extracellular matrix (ECM) microenvironment. Numerous studies have demonstrated that extracellular cues, including topological, mechanical, and biochemical properties of the underlying substrates, dictate the chondrocyte behaviors. Consequently, developing advanced biomaterials with the desired characteristics which could achieve the biointerface between cells and the surrounded matrix close to the physiological conditions becomes a great hotspot in bioengineering.

Osteoporosis-decreased extracellular matrix stiffness impairs connexin 43-mediated gap junction intercellular communication in osteocytes.

Osteocytes are the main sensitive and responsive cells for mechanical stimuli in bone. The connexin family enables them to communicate with each other via forming functional gap junctions. However, how osteoporosis-impaired extracellular mechanical property modulates gap junction intercellular communication in osteocytes remains elusive.

Aberrant activation of latent transforming growth factor-β initiates the onset of temporomandibular joint osteoarthritis.

There is currently no effective medical treatment for temporomandibular joint osteoarthritis (TMJ-OA) due to a limited understanding of its pathogenesis. This study was undertaken to investigate the key role of transforming growth factor-β (TGF-β) signalling in the cartilage and subchondral bone of the TMJ using a temporomandibular joint disorder (TMD) rat model, an ageing mouse model and a Camurati-Engelmann disease (CED) mouse model. In the three animal models, the subchondral bone phenotypes in the mandibular condyles were evaluated by µCT, and changes in TMJ condyles were examined by TRAP staining and immunohistochemical analysis of Osterix and p-Smad2/3.

Evidence for excessive osteoclast activation in SIRT6 null mice.

SIRT6 is a NAD-dependent histone 3 deacetylase. SIRT6 null mice have been reported suffering osteopenia. However, the role of SIRT6 in bone resorption is still not well understood.

Bivalent Histone Modifications and Development.

Background: Development is an epigenetic regulation dependent event. As one pretranscriptional regulator, bivalent histone modifications were observed to be involved in development recently. It is believed that histone methylation potentially takes charge of cell fate determination and differentiation.

Spatial signalling mediated by the transforming growth factor-β signalling pathway during tooth formation.

Tooth development relies on sequential and reciprocal interactions between the epithelial and mesenchymal tissues, and it is continuously regulated by a variety of conserved and specific temporal-spatial signalling pathways. It is well known that suspensions of tooth germ cells can form tooth-like structures after losing the positional information provided by the epithelial and mesenchymal tissues. However, the particular stage in which the tooth germ cells start to form tooth-like structures after losing their positional information remains unclear.

BMP7 and EREG Contribute to the Inductive Potential of Dental Mesenchyme.

Odontogenesis is accomplished by reciprocal signaling between the epithelial and mesenchymal compartments. It is generally accepted that the inductive mesenchyme is capable of inducing the odontogenic commitment of both dental and non-dental epithelial cells. However, the duration of this signal in the developing dental mesenchyme and whether adult dental pulp tissue maintains its inductive capability remain unclear.

Epigenetic Control of Gene Function in Enamel Development.

Amelogenesis consists of various development phases that are tightly controlled by the exquisitely sequential and reciprocal interactions between tooth epithelium and mesenchyme. Subtle alterations during this complex physiological and biochemical development events could lead to severe enamel defects in shape, color and structure. Modulations in microRNA, DNA methylation and chromatin modifications are emerging as important regulatory mechanisms during tooth development.

The expression and function of microRNAs in bone homeostasis.

microRNAs (miRNAs) are a class of small, endogenous, non-coding single strand RNAs. miRNAs are involve in multiple developmental events during embryogenesis and adult tissue homeostasis. miRNAs regulate epigenetic regulating genes through post-transcriptional regulation and that epigenetic factors mediate the regulation of miRNA.