Osteoclasts: Multifaceted Molecule in Vesicular Trafficking

Kanakamedala, Anil Kumar; Mahendra, Jaideep; Kareem, Nashra; Mahendra, Little

doi:10.7860/jcdr/2019/40307.13064

Cited by 1 publication

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“…The c-Jun N-terminal kinase (JNK) signaling pathway mobilizes osteoclastic transcription factors associated with c-Fos antigens (Fra-1 and 2) / NFATc1, another pathway is extracellular signal-regulated kinase 1 (ERK1) / NF-kB / activator protein 1 (AP-1) / MITF and p38 / AP-1 / MITF signaling (Fig. 3) (Boyce & Xing, 2008;Kanakamedala et al, 2019;Soysa & Alles, 2019).…”

Section: Fig 2 Schematic Representation Of a Basic Multicellular Unit (Bmu)mentioning

confidence: 99%

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Bone remodeling stages under physiological conditions and glucocorticoid in excess: Focus on cellular and molecular mechanisms

Povoroznyuk

Dedukh

Bystrytska

et al. 2021

Regul. Mech. Biosyst.

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This review provides a rationale for the cellular and molecular mechanisms of bone remodeling stages under physiological conditions and glucocorticoids (GCs) in excess. Remodeling is a synchronous process involving bone resorption and formation, proceeding through stages of: (1) resting bone, (2) activation, (3) bone resorption, (4) reversal, (5) formation, (6) termination. Bone remodeling is strictly controlled by local and systemic regulatory signaling molecules. This review presents current data on the interaction of osteoclasts, osteoblasts and osteocytes in bone remodeling and defines the role of osteoprogenitor cells located above the resorption area in the form of canopies and populating resorption cavities. The signaling pathways of proliferation, differentiation, viability, and cell death during remodeling are presented. The study of signaling pathways is critical to understanding bone remodeling under normal and pathological conditions. The main signaling pathways that control bone resorption and formation are RANK / RANKL / OPG; M-CSF – c-FMS; canonical and non-canonical signaling pathways Wnt; Notch; MARK; TGFβ / SMAD; ephrinB1/ephrinB2 – EphB4, TNFα – TNFβ, and Bim – Bax/Bak. Cytokines, growth factors, prostaglandins, parathyroid hormone, vitamin D, calcitonin, and estrogens also act as regulators of bone remodeling. The role of non-encoding microRNAs and long RNAs in the process of bone cell differentiation has been established. MicroRNAs affect many target genes, have both a repressive effect on bone formation and activate osteoblast differentiation in different ways. Excess of glucocorticoids negatively affects all stages of bone remodeling, disrupts molecular signaling, induces apoptosis of osteocytes and osteoblasts in different ways, and increases the life cycle of osteoclasts. Glucocorticoids disrupt the reversal stage, which is critical for the subsequent stages of remodeling. Negative effects of GCs on signaling molecules of the canonical Wingless (WNT)/β-catenin pathway and other signaling pathways impair osteoblastogenesis. Under the influence of excess glucocorticoids biosynthesis of biologically active growth factors is reduced, which leads to a decrease in the expression by osteoblasts of molecules that form the osteoid. Glucocorticoids stimulate the expression of mineralization inhibitor proteins, osteoid mineralization is delayed, which is accompanied by increased local matrix demineralization. Although many signaling pathways involved in bone resorption and formation have been discovered and described, the temporal and spatial mechanisms of their sequential turn-on and turn-off in cell proliferation and differentiation require additional research.

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Section: Fig 2 Schematic Representation Of a Basic Multicellular Unit (Bmu)mentioning

confidence: 99%

“…6) (Feng & Teitelbaum, 2013;Teitelbaum, 2015). In addition to adhesion, integrin αvβ3 is involved in osteoclast migration (Mellis et al, 2011;Kanakamedala et al, 2019). The formation and function of actin that makes up the osteoclast cytoskeleton is regulated by Rho family proteins (GTPases).…”

Section: Figmentioning

confidence: 99%