HIF1 activation safeguards cortical bone formation against impaired oxidative phosphorylation.

Energy metabolism, through pathways such as oxidative phosphorylation (OxPhos) and glycolysis, plays a pivotal role in cellular differentiation and function. Our study investigates the impact of OxPhos disruption in cortical bone development by deleting mitochondrial transcription factor A (TFAM). TFAM controls OxPhos by regulating the transcription of mitochondrial genes.

Osteoblastic erythropoietin is not required for bone mass accrual.

Erythropoietin (EPO), primarily produced by interstitial fibroblasts in the kidney during adulthood, and its receptor are well-known for their crucial role in regulating erythropoiesis. Recent research has unveiled an additional function of circulating EPO in the control of bone mass accrual and homeostasis through its receptor, which is expressed in both osteoblasts and osteoclasts. Notably, cells of the osteoblast lineage can produce and secrete functional EPO upon activation of the hypoxia signaling pathway.

Reduced Bone Mass in Collagen Prolyl 4-Hydroxylase ; Compound Mutant Mice.

Proper deposition of the extracellular matrix and its major components, the collagens, is essential for endochondral ossification and bone mass accrual. Collagen prolyl 4-hydroxylases (C-P4Hs) hydroxylate proline residues in the -X-Pro-Gly- repeats of all known collagen types. Their product, 4-hydroxyproline, is essential for correct folding and thermal stability of the triple-helical collagen molecules in physiological body temperatures.

Fetal Growth Plate Cartilage : Histological and Immunohistochemical Techniques.

Skeletal development is a tightly regulated process that primarily occurs through two distinct mechanisms. In intramembranous ossification, mesenchymal progenitors condense and transdifferentiate directly into osteoblasts, giving rise to the flat bones of the skull. The majority of the skeleton develops through endochondral ossification, in which mesenchymal progenitors give rise to a cartilaginous template that is gradually replaced by bone.

Suppressing Mitochondrial Respiration Is Critical for Hypoxia Tolerance in the Fetal Growth Plate.

Oxygen (O) is both an indispensable metabolic substrate and a regulatory signal that controls the activity of Hypoxia-Inducible Factor 1α (Hif1a), a mediator of the cellular adaptation to low O tension (hypoxia). Hypoxic cells require Hif1a to survive. Additionally, Hif1a is an inhibitor of mitochondrial respiration.

Hypoxia-inducible factor 2α is a negative regulator of osteoblastogenesis and bone mass accrual.

Osteoblasts, which are the bone-forming cells, operate in a hypoxic environment. The transcription factors hypoxia-inducible factor-1α (HIF1) and HIF2 are key mediators of the cellular response to hypoxia. Both are expressed in osteoblasts.

Bicarbonate Recycling by HIF-1-Dependent Carbonic Anhydrase Isoforms 9 and 12 Is Critical in Maintaining Intracellular pH and Viability of Nucleus Pulposus Cells.

Intervertebral disc degeneration is a ubiquitous condition closely linked to chronic low-back pain. The health of the avascular nucleus pulposus (NP) plays a crucial role in the development of this pathology. We tested the hypothesis that a network comprising HIF-1α, carbonic anhydrase (CA) 9 and 12 isoforms, and sodium-coupled bicarbonate cotransporters (NBCs) buffer intracellular pH through coordinated bicarbonate recycling.

Olive and grape seed extract prevents post-traumatic osteoarthritis damages and exhibits in vitro anti IL-1β activities before and after oral consumption.

Polyphenols exert a large range of beneficial effects in the prevention of age-related diseases. We sought to determine whether an extract of olive and grape seed standardized according to hydroxytyrosol (HT) and procyanidins (PCy) content, exerts preventive anti-osteoathritic effects. To this aim, we evaluated whether the HT/PCy mix could (i) have in vitro anti-inflammatory and chondroprotective actions, (ii) exert anti-osteoarthritis effects in two post-traumatic animal models and (iii) retain its bioactivity after oral administration.

Osteoarthritis: from pathogenic mechanisms and recent clinical developments to novel prospective therapeutic options.

Osteoarthritis (OA) is a degenerative joint disease that, despite recent progress, has no curative treatment. Considerable research has recently been initiated to identify new potential therapeutic targets. In this review, we will set forth some of the major discoveries in the past 5 years, notably those dealing with the identification of pathogenic factors [hypoxia-inducible factors (HIFs), complement, transforming growth factor (TGF)-β and zinc-ZIP8].

Hypoxia promotes noncanonical autophagy in nucleus pulposus cells independent of MTOR and HIF1A signaling.

Nucleus pulposus (NP) cells reside in the avascular and hypoxic microenvironment of intervertebral discs. Importantly, many activities related to survival and function of NP cells are controlled by the HIF-family of transcription factors. We hypothesize that NP cells adapt to their hypoxic niche through modulation of macroautophagy/autophagy.

Analysis of Mouse Growth Plate Development.

To investigate skeletal development, pathophysiological mechanisms of cartilage and bone disease, and eventually assess innovative treatments, the mouse is a very important resource. During embryonic development, mesenchymal condensations are formed, and cells within these mesenchymal condensations either directly differentiate into osteoblasts and give origin to intramembranous bone, or differentiate into chondrocytes and form a cartilaginous anlage. The cartilaginous anlage or fetal growth plate is then replaced with bone.

Fibrosis and hypoxia-inducible factor-1α-dependent tumors of the soft tissue on loss of von Hippel-Lindau in mesenchymal progenitors.

The hypoxia-inducible factor (Hif)-1α (Hif-1α) and Hif-2α (Epas1) have a critical role in both normal development and cancer. von Hippel Lindau (Vhl) protein, encoded by a tumor suppressor gene, is an E3 ubiquitin ligase that targets Hif-1α and Epas1 to the proteasome for degradation. To better understand the role of Vhl in the biology of mesenchymal cells, we analyzed mutant mice lacking Vhl in mesenchymal progenitors that give rise to the soft tissues that form and surround synovial joints.

HIF-1α and growth plate development: what we really know.

Adaptation to low oxygen tension or hypoxia is a critical event in development and tissue homeostasis. Studies by us and others have shown that the fetal growth plate is an avascular tissue with a gradient of oxygenation, and the transcription factor hypoxia-inducible factor-1α (HIF-1α) is essential for its development. In this brief review, we will summarize our current understanding of the role of HIF-1α in fetal growth plate development, and we will discuss yet unanswered questions in the field of hypoxia and endochondral bone formation.

Direct comparison of current cell-based and cell-free approaches towards the repair of craniofacial bone defects - A preclinical study.

Unlabelled: For craniofacial bone defect repair, several alternatives to bone graft (BG) exist, including the combination of biphasic calcium phosphate (BCP) biomaterials with total bone marrow (TBM) and bone marrow-derived mesenchymal stromal cells (MSCs), or the use of growth factors like recombinant human bone morphogenic protein-2 (RhBMP-2) and various scaffolds. Therefore, clinicians might be unsure as to which approach will offer their patients the most benefit. Here, we aimed to compare different clinically relevant bone tissue engineering methods in an "all-in-one" study in rat calvarial defects.

Inverse regulation of early and late chondrogenic differentiation by oxygen tension provides cues for stem cell-based cartilage tissue engineering.

Background/aims: Multipotent stem/stromal cells (MSC) are considered promising for cartilage tissue engineering. However, chondrogenic differentiation of MSC can ultimately lead to the formation of hypertrophic chondrocytes responsible for the calcification of cartilage. To prevent the production of this calcified matrix at the articular site, the late hypertrophic differentiation of MSCs must be carefully controlled.

Loss of HIF-1α in the notochord results in cell death and complete disappearance of the nucleus pulposus.

The intervertebral disc (IVD) is one of the largest avascular organs in vertebrates. The nucleus pulposus (NP), a highly hydrated and proteoglycan-enriched tissue, forms the inner portion of the IVD. The NP is surrounded by a multi-lamellar fibrocartilaginous structure, the annulus fibrosus (AF).

Loss of VHL in mesenchymal progenitors of the limb bud alters multiple steps of endochondral bone development.

Adaptation to low oxygen tension (hypoxia) is a critical event during development. The transcription factors Hypoxia Inducible Factor-1α (HIF-1α) and HIF-2α are essential mediators of the homeostatic responses that allow hypoxic cells to survive and differentiate. Von Hippel-Lindau protein (VHL) is the E3 ubiquitin ligase that targets HIFs to the proteasome for degradation in normoxia.

Nutraceuticals in joint health: animal models as instrumental tools.

Osteoarthritis (OA) is a degenerative joint disease with no curative treatments. Many studies have begun to demonstrate the efficacy of nutraceuticals for slowing down OA. Animal models are utilized as a compulsory step in demonstrating the protective potential of these compounds on joint health.

Determining a clinically relevant strategy for bone tissue engineering: an "all-in-one" study in nude mice.

Purpose: Autologous bone grafting (BG) remains the standard reconstruction strategy for large craniofacial defects. Calcium phosphate (CaP) biomaterials, such as biphasic calcium phosphate (BCP), do not yield consistent results when used alone and must then be combined with cells through bone tissue engineering (BTE). In this context, total bone marrow (TBM) and bone marrow-derived mesenchymal stem cells (MSC) are the primary sources of cellular material used with biomaterials.

Effects of in vitro low oxygen tension preconditioning of adipose stromal cells on their in vivo chondrogenic potential: application in cartilage tissue repair.

Purpose: Multipotent stromal cell (MSC)-based regenerative strategy has shown promise for the repair of cartilage, an avascular tissue in which cells experience hypoxia. Hypoxia is known to promote the early chondrogenic differentiation of MSC. The aim of our study was therefore to determine whether low oxygen tension could be used to enhance the regenerative potential of MSC for cartilage repair.

Health claims assessment in the field of joint and cartilage: a consensus viewpoint of the Group for the Respect of Ethics and Excellence in Science.

Introduction: In 2006, the European Parliament and Council issued a regulation (No. 1924/2006) for the nutrition and health claims made on foods, including food supplements. According to the regulation, the use of nutrition and health claims shall only be permitted if the substance in respect of which the claim is made has been shown to have a beneficial nutritional or physiological effect.

Pharmacological modulation of human mesenchymal stem cell chondrogenesis by a chemically oversulfated polysaccharide of marine origin: potential application to cartilage regenerative medicine.

Mesenchymal stem cells (MSCs) are considered as an attractive source of cells for cartilage engineering due to their availability and capacity for expansion and multipotency. Differentiation of MSC into chondrocytes is crucial to successful cartilage regeneration and can be induced by various biological agents, including polysaccharides that participate in many biological processes through interactions with growth factors. Here, we hypothesize that growth factor-induced differentiation of MSC can be increased by chemically oversulfated marine polysaccharides.

Sterilization of exopolysaccharides produced by deep-sea bacteria: impact on their stability and degradation.

Polysaccharides are highly heat-sensitive macromolecules, so high temperature treatments are greatly destructive and cause considerable damage, such as a great decrease in both viscosity and molecular weight of the polymer. The technical feasibility of the production of exopolysaccharides by deep-sea bacteria Vibrio diabolicus and Alteromonas infernus was previously demonstrated using a bioproduct manufacturing process. The objective of this study was to determine which sterilization method, other than heat sterilization, was the most appropriate for these marine exopolysaccharides and was in accordance with bioprocess engineering requirements.

The effect of two- and three-dimensional cell culture on the chondrogenic potential of human adipose-derived mesenchymal stem cells after subcutaneous transplantation with an injectable hydrogel.

Articular cartilage is an avascular tissue composed of chondrocytes, a unique cell type responsible for abundant matrix synthesis and maintenance. When damaged, it never heals spontaneously under physiological circumstances. Therefore, the delivery of mesenchymal stem cells using hydrogel has been considered for cartilage repair.