Signal Transduction Cascades Controlling Osteoblast Differentiation

Gorter, David J. J. de; Sánchez‐Duffhues, Gonzalo; Dijke, Peter ten

doi:10.1002/9781119266594.ch7

Cited by 4 publications

(7 citation statements)

References 37 publications

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“…Osteoblasts are under the tight control of paracrine, autocrine and endocrine signals. In fact, virtually all common signal transduction pathways converge on osteoblasts regulating their homeostasis (de Gorter DJJ & ten Dijke P 2013). …”

Section: Biogenesis and Function Of Bone Cellsmentioning

confidence: 99%

“…Key transcription factors for osteoblast differentiation are osterix and RUNX2; the former is often used to regulate cre recombinase for osteoblast-specific gene expression (Blair et al 2008). The molecular pathways that are responsible for osteoblast differentiation, proliferation and ultimately apoptosis are complex (de Gorter DJJ & ten Dijke P 2013). Among the most thoroughly studied and potent regulators of osteoblast differentiation are the mitogen activated kinases (MAPK), the Wnt/β-catenin, the bone morphogenic proteins (BMP) and transforming growth factor-β (TGFβ), the Hedgehog, the Notch, the insulin-like growth factor 1(IGF1), the fibroblast growth factor (FGF) and the Calcium signal transduction pathways that ultimately converge on RUNX2, which is the master regulator of osteoblast differentiation (Blair et al in press).…”

Section: Biogenesis and Function Of Bone Cellsmentioning

confidence: 99%

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High-density lipoprotein (HDL) metabolism and bone mass

Papachristou

Blair

Kypreos

et al. 2017

Journal of Endocrinology

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It is well appreciated that high density lipoprotein (HDL) and bone physiology and pathology are tightly linked. Studies, primarily in mouse models have shown that dysfunctional and/or disturbed HDL can affect bone mass through many different ways. Specifically, reduced HDL levels have been associated with the development of an inflammatory microenvironment that affects the differentiation and function of osteoblasts. In addition, perturbation in HDL metabolic pathways favor adipoblastic and restrain osteoblastic differentiation through, among others, the modification of specific bone-related chemokines and signaling cascades. Increased bone marrow adiposity also deteriorates bone osteoblastic function and thus bone synthesis, leading to reduced bone mass. In this review, we present the current knowledge and the future directions with regards to the HDL-bone mass connection. Unraveling the molecular phenomena that underline this connection will promote the deeper understanding of the pathophysiology of bone-related pathologies, such as osteoporosis or bone metastasis, and pave the way towards the development of novel more effective therapies against these conditions.

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Section: Biogenesis and Function Of Bone Cellsmentioning

confidence: 99%

Section: Biogenesis and Function Of Bone Cellsmentioning

confidence: 99%

High-density lipoprotein (HDL) metabolism and bone mass

Papachristou

Blair

Kypreos

et al. 2017

Journal of Endocrinology

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“…Notably, osteoblast differentiation and function is influenced by nearly all the common signal transduction pathways implicated in cell homeostasis [13]. The master regulators of osteoblastic differentiation are osterix and RUNX2; RUNX2 is an upstream osterix effector that regulate cre-recombinase for osteoblast-specific gene expression [14]. The signaling cascades implicated in osteoblast differentiation, proliferation and ultimately apoptosis are numerous and overlapping and include the mitogen-activated kinases (MAPK), the Wnt/β-catenin, the bone morphogenic proteins (BMP) and transforming growth factor-β (TGFβ), the hedgehog, the Notch, the insulin-like growth factor 1(IGF1), the fibroblast growth factor (FGF) and the calcium signal transduction pathways that regulate RUNX2 [15].…”

Section: Figurementioning

confidence: 99%

“…The osteolytic function of OCLs is facilitated by the secretion of acid proteinases, such as cathepsins K and matrix metalloproteases (MMP)-9 and -13 that degrade collagen fibers. Bone debris are removed chiefly by vacuolar translocation [14]. It is noteworthy that OCL differentiation and maturation is highly dependent upon OBL.…”

Section: Figurementioning

confidence: 99%

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Insights into the Cellular and Molecular Mechanisms That Govern the Fracture-Healing Process: A Narrative Review

Papachristou

Georgopoulos

Giannoudis

et al. 2021

JCM

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Fracture-healing is a complex multi-stage process that usually progresses flawlessly, resulting in restoration of bone architecture and function. Regrettably, however, a considerable number of fractures fail to heal, resulting in delayed unions or non-unions. This may significantly impact several aspects of a patient’s life. Not surprisingly, in the past few years, a substantial amount of research and number of clinical studies have been designed, aiming at shedding light into the cellular and molecular mechanisms that regulate fracture-healing. Herein, we present the current knowledge on the pathobiology of the fracture-healing process. In addition, the role of skeletal cells and the impact of marrow adipose tissue on bone repair is discussed. Unveiling the pathogenetic mechanisms that govern the fracture-healing process may lead to the development of novel, smarter, and more effective therapeutic strategies for the treatment of fractures, especially of those with large bone defects.

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Bone and the Unfolded Protein Response: In Sickness and in Health

Iyer

Adams

2023

Calcif Tissue Int

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Differentiation and optimal function of osteoblasts and osteoclasts are contingent on synthesis and maintenance of a healthy proteome. Impaired and/or altered secretory capacity of these skeletal cells is a primary driver of most skeletal diseases. The endoplasmic reticulum (ER) orchestrates the folding and maturation of membrane as well as secreted proteins at high rates within a calcium rich and oxidative organellar niche. Three ER membrane proteins monitor fidelity of protein processing in the ER and initiate an intricate signaling cascade known as the Unfolded Protein Response (UPR) to remediate accumulation of misfolded proteins in its lumen, a condition referred to as ER stress. The UPR aids in fine-tuning, expanding and/or modifying the cellular proteome, especially in specialized secretory cells, to match everchanging physiologic cues and metabolic demands. Sustained activation of the UPR due to chronic ER stress, however, is known to hasten cell death and drive pathophysiology of several diseases. A growing body of evidence suggests that ER stress and an aberrant UPR may contribute to poor skeletal health and the development of osteoporosis. Small molecule therapeutics that target distinct components of the UPR may therefore have implications for developing novel treatment modalities relevant to the skeleton. This review summarizes the complexity of UPR actions in bone cells in the context of skeletal physiology and osteoporotic bone loss, and highlights the need for future mechanistic studies to develop novel UPR therapeutics that mitigate adverse skeletal outcomes.

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Signal Transduction Cascades Controlling Osteoblast Differentiation

Cited by 4 publications

References 37 publications

High-density lipoprotein (HDL) metabolism and bone mass

High-density lipoprotein (HDL) metabolism and bone mass

Insights into the Cellular and Molecular Mechanisms That Govern the Fracture-Healing Process: A Narrative Review

Bone and the Unfolded Protein Response: In Sickness and in Health

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