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Skeletal Mechanobiology
Published in Jiro Nagatomi, Eno Essien Ebong, Mechanobiology Handbook, 2018
Alesha B. Castillo, Christopher R. Jacobs
Guanine nucleotide-binding (G)-protein-coupled receptors (GPCRs) are the largest family of membrane receptors and are activated by biochemical and mechanical stimuli.169,170 They play a critical role in a variety of cellular processes including proliferation, migration, and chemotaxis. GPCRs contain α, β, and γ subunits, and four main classes of Gα proteins (Gs, Gi/o, Gq/11, and G12/13) engage unique downstream targets when activated. Gs activates cAMP, protein kinase A (PKA), and mitogen-activated protein kinase (MAPK) signaling—Gi activates Src and PI3K signaling, Gq/11 activates phospholipase C (PLC)/ protein kinase C (PKC) signaling, and G12/13 can activate Rho GTP binding proteins. Mice, with an osteoblast-specific ablation of Gs171 and Gi172 in osteoblasts, exhibited significantly reduced cortical and trabecular bone volume, whereas an overexpression of Gs in osteoblasts results in a significant increase in bone mass.173 Frangos and colleagues recently showed that osteoblasts expose to fluid flow undergo a conformational change in PTH1R, a G-protein-coupled receptor, in a ligand-independent manner.174 They have also shown that a flow-induced activation of G-proteins independent of the membrane receptor is possible. Additional data are needed to further explore the role of G-protein-coupled receptors bone cell mechanotransduction.
Dendritic Polymers for the Repair of Tissues
Published in Delphine Felder-Flesch, Dendrimers in Nanomedicine, 2016
Cynthia Ghobril, Mark W. Grinstaff
excessive swelling can cause tissue compression, or detachment of the gel from the wound site. However, at higher PAMAM: PLA-PEG-PLA ratios (e.g., 0.5, 1, and 2), intramolecular and/or intermolecular crosslinking between the acryloyl groups on PAMAM dendrimers can also occur leading to softer hydrogels. Extended degradation times of hydrogels were observed with increasing PAMAM:PLA-PEG-PLA ratios in the scaffolds. For example, PLA-PEG-PLA hydrogels degraded in 27 days whereas the degradation time of PAMAM/PLA-PEG-PLA hydrogels at a PAMAM: PLA-PEG-PLA ratio of 1/10, 1/5, 1/2, and 1/1 was measured to be 30, 36, 39, and 45 days, respectively. Next, mouse bone marrow mesenchymal stem cells (mMSCs) were encapsulated in hydrogels at a PAMAM:PLA-PEG-PLA ratio of 1/5 to evaluate whether they can stimulate stem-cells proliferation and differentiation, similarly to ECMs of native tissues. It was observed that hydrogels with RGDyC moieties increased cell attachment and proliferation, whereas hydrogels without RGDyC caused reduction in cell viability. Moreover, it was reported that the activation of a5ji1 integrin receptor in mMSCs can be triggered by RGDyC, which further promotes osteogenic differentiation and leads to bone tissue regeneration. Consequently, enhanced gene expression of osteogenic markers of mMSC differentiation such as alkaline phosphatase (ALP), osterix (OSX), parathyroid hormone 1 receptor (PTH1R), and osteocalcin (OC) was observed by real-time polymerase chain reaction (PCR) in cells cultured within the bioactive hydrogels at 4 and 7 days, as compared to hydrogels without RGDyC moieties. The enhanced promotion of mMSCs proliferation and differentiation within PAMAM/PLA-PEG-PLA hydrogels due to the presence of multivalent RGDyC moieties supported the strategy of using dendritic macromolecules for the introduction of these bioactive molecules, and further demonstrated the potential use of these materials in tissue engineering.
Marine sources as an unexplored bone tissue reconstruction material -A review
Published in Egyptian Journal of Basic and Applied Sciences, 2022
Gayatree Nayak, Sanat Kumar Bhuyan, Ruchi Bhuyan, Akankshya Sahu, Dattatreya Kar, Ananya Kuanar
The organic and inorganic bioactive molecules of marine sources play a pivotal role in the formation of osteoblasts in the presence of c-Fms, M-CSF, and OPG, that is prevented the binding of RANK and RANKL signaling pathways and helps the proliferation and survival of osteoblast. The NO acts as a positive inducer for osteoblast formation through eNOs. The prostaglandinE2 (PGE2) can activate EP2 to inhibit cAMP while EP3 activates cAMP through α3-GTP, the cAMP is induced the bone formation by PKA and CREB, PGE2 inhibits osteoblast through EP1, PLC-γ, and Ca2+ channel. The parathyroid hormone (PTH) promotes osteoblast by PTH1R and inhibits osteoclast in the presence of OPG (-) and RANKL (+) pathways. The 25(OH)D3can activate 1α,25(OH)2D3, which stimulates bone calcification via downregulation of RUNX2anddirectly promotes bone resorption. On other hand, the organic and inorganic bioactive molecules of marine sources are sometimes released cytokines and growth factors that are responsible for the binding of RANK and RANKL signaling pathways and lead to preosteoclasts after that their fusion to form osteoclasts by activating growth factors like TGF-β, IGFs, FGFs, PDGFs, BMPs. The coral reef releases palytoxin which is responsible for activating osteoclast. The molecular mechanism of bone regeneration in Figure 4.
Effects of running a marathon on sclerostin and parathyroid hormone concentration in males aged over 50
Published in Journal of Sports Sciences, 2023
Aleksandra Zagrodna, Anna Książek, Małgorzata Słowińska-Lisowska, Jan Chmura, Piotr Ponikowski, Giovanni Lombardi
Expression of sclerostin is also subjected to a strict endocrine regulation and, among the hormones parathyroid hormone (PTH) is of particular relevance since it is a master regulator of calcium metabolism (Sims & Chia, 2012). Parathyroid hormone is an 84-amino acid peptide hormone synthesized in the chief cells of the parathyroid glands. It is essential for the maintenance of serum calcium concentration within a narrow range through direct actions on bone, kidney, and, indirectly, on small intestine (Anastasilakis et al., 2014). Parathyroid hormone acts via the parathyroid hormone 1 receptor (PTH1R) expressed by mesenchymal stem cells and cells of the osteoblastic lineage (eg osteoprogenitors, lining cells, immature and mature osteoblasts, and osteocytes). Parathyroid hormone stimulates proliferation, osteoblast differentiation, osteoblast activity, ECM deposition, and mineralisation. However, PTH can also induce the expression of the tumour-necrosis factor (TNF)-related ligand of the receptor activator of nuclear factor κB (RANκL) that stimulates osteoclast differentiation and activity via RANκ, and inhibits osteoprotegerin, a decoy receptor for RANκL. Osteoclast activity causes the release of calcium (Ca2+) from the resorbing bone, which, in turn, inhibits the expression of PTH in the parathyroid glands (Lombardi et al., 2020). While PTH stimulates both bone resorption and bone formation, the final outcome on bone mass, catabolic or anabolic, depends on the dose and periodicity of the PTH signal. Continuous exposure to PTH results in catabolic effects on the skeleton, while intermittent, low doses of PTH result in osteoanabolic effects (Miyamoto-Mikami et al., 2015). Parathyroid hormone negatively regulates sclerostin expression in rodent bone tissue (Gardinier et al., 2015), and serum sclerostin concentrations in humans (Yu et al., 2011). Parathyroid hormone responses to acute exercise stimuli in humans show variable patterns depending on the type of exercise (Lombardi et al., 2020). The available literature contains little available data on changes in PTH concentration during the postexercise period caused by long-term stimulus, and such studies on the middle-aged population have not yet been published.