Osteoporosis: From Molecular Mechanisms to Therapies

Tang, Chih‐Hsin

doi:10.3390/ijms21030714

Cited by 15 publications

(10 citation statements)

References 16 publications

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“…By contrast, RANKL is typically expressed by osteoblasts; it binds to RANK present on osteoclast precursors [22]. The RANK/RANKL signaling pathway promotes osteoclast survival and TRAFs 2, 5, and 6 that transduce signals to activate the NF-kB and JNK pathways [32]. We previously demonstrated that synovial IL-16 is a novel biomarker for PJI diagnosis [33].…”

Section: Discussionmentioning

confidence: 99%

Synovial Fluid Interleukin-16 Contributes to Osteoclast Activation and Bone Loss through the JNK/NFATc1 Signaling Cascade in Patients with Periprosthetic Joint Infection

Chang

Hsiao

et al. 2020

IJMS

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Because of lipopolysaccharide (LPS)-mediated effects on osteoclast differentiation and bone loss, periprosthetic joint infection (PJI) caused by Gram-negative bacteria increases the risk of aseptic loosening after reimplantation. Synovial fluid interleukin-16 (IL-16) expression was higher in patients with PJI than in patients without joint infection. Thus, we explored the effects of IL-16 on bone. We investigated whether IL-16 modulates osteoclast or osteoblast differentiation in vitro. An LPS-induced bone loss mice model was used to explore the possible advantages of IL-16 inhibition for the prevention of bone loss. IL-16 directly activated p38 and c-Jun N-terminal kinase (JNK)/mitogen-activated protein kinase (MAPK) signaling and increased osteoclast activation markers, including tartrate-resistant acid phosphatase (TRAP), cathepsin K, and nuclear factor of activated T cells 1 (NFATc1). IL-16 directly caused monocytes to differentiate into TRAP-positive osteoclast-like cells through NFATc1 activation dependent on JNK/MAPK signaling. Moreover, IL-16 did not alter alkaline phosphatase activity or calcium deposition during osteoblastic differentiation. Finally, IL-16 inhibition prevented LPS-induced trabecular bone loss and osteoclast activation in vivo. IL-16 directly increased osteoclast activation through the JNK/NFATc1 pathway. IL-16 inhibition could represent a new strategy for treating infection-associated bone loss.Int. J. Mol. Sci. 2020, 21, 2904 2 of 15 of differentiation 4 (CD4 + ) lymphocytes, monocytes, and eosinophils [11,12]. IL-16 is synthesized as a precursor protein (pro-IL-16) of approximately 68 kDa. Pro-IL-16 is cleaved by activated caspase-3 and then IL-16 generation [13]. CD4 serves as a signaling transducing receptor for IL-16 signaling. Increased intracytoplasmic calcium and inositol trisphosphate can be initiated when IL-16 interacts with CD4 receptors, and this subsequently activates stress-activated protein kinases (SAPKs) p46 and p54. Stimulation with IL-16 also activates members of the mitogen-activated protein kinase (MAPK) family, namely c-Jun N-terminal kinase (JNK) and p38 but does not activate extracellular signal-regulated kinase (ERK)-1 or ERK-2 [14]. IL-16 can activate monocytes and stimulate the secretion of inflammatory cytokines, chiefly tumor necrosis factor (TNF)-α, IL-1β, 15,16]. Currently, these cytokines are believed to promote the development of septic arthritis [17][18][19].PJI can result from Gram-positive (GP) or Gram-negative (GN) bacterial infections. Our previous retrospective study revealed that GN infections were associated with an increased risk of aseptic loosening as compared with GP infections [20]. The cell walls of GP bacteria contain lipoteichoic acid (LTA) components, whereas those of GN bacteria contain components of lipopolysaccharide (LPS). In studies of mice receiving intrafemoral injections of LPS or LTA, LPS reduced both the number of trabeculae and bone mineral density, whereas LTA did not have this effect [20]. In addition, disruption of the bal...

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Section: Discussionmentioning

confidence: 99%

Synovial Fluid Interleukin-16 Contributes to Osteoclast Activation and Bone Loss through the JNK/NFATc1 Signaling Cascade in Patients with Periprosthetic Joint Infection

Chang

Hsiao

et al. 2020

IJMS

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“…Osteoporosis is one of the most common metabolic bone diseases which results from the disrupted balance between bone formation and resorption 1 . With the progressive aging of the global population, the incidence of osteoporosis is increasing dramatically which leads to an increased risk of fractures and exerts a strong impact on morbidity, and even mortality 2,3 . However, the pathological mechanisms of osteoporosis have not been fully understood yet.…”

Section: Introductionmentioning

confidence: 99%

Long non-coding RNA MIR22HG promotes osteogenic differentiation of bone marrow mesenchymal stem cells via PTEN/ AKT pathway

et al. 2020

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Osteoporosis is a prevalent metabolic bone disease characterized by low bone mineral density and degenerative disorders of bone tissues. Previous studies showed the abnormal osteogenic differentiation of endogenous bone marrow mesenchymal stem cells (BMSCs) contributes to the development of osteoporosis. However, the underlying mechanisms by which BMSCs undergo osteogenic differentiation remain largely unexplored. Recently, long non-coding RNAs have been discovered to play important roles in regulating BMSC osteogenesis. In this study, we first showed MIR22HG, which has been demonstrated to be involved in the progression of several cancer types, played an important role in regulating BMSC osteogenesis. We found the expression of MIR22HG was significantly decreased in mouse BMSCs from the osteoporotic mice and it was upregulated during the osteogenic differentiation of human BMSCs. Overexpression of MIR22HG in human BMSCs enhanced osteogenic differentiation, whereas MIR22HG knockdown inhibited osteogenic differentiation both in vitro and in vivo. Mechanistically, MIR22HG promoted osteogenic differentiation by downregulating phosphatase and tensin homolog (PTEN) and therefore activating AKT signaling. Moreover, we found MIR22HG overexpression promoted osteoclastogenesis of RAW264.7 cells, which indicated that MIR22HG played a significant role in bone metabolism and could be a therapeutic target for osteoporosis and other bone-related diseases.

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“… 1 Heredity, hormone levels, nutrition, and lifestyle are closely related to the pathogenesis of OP. 2 - 4 Oestrogen, parathyroid hormone, vitamin D, and inflammatory factors are all important regulators of bone metabolism. Although many aetiologies have been identified, the pathogenesis of OP is still being explored.…”

Section: Introductionmentioning

confidence: 99%

Gut microbiome and osteoporosis

Mao

Zhou

et al. 2020

Bone & Joint Research

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Osteoporosis (OP) is a chronic metabolic bone disease characterized by the decrease of bone tissue per unit volume under the combined action of genetic and environmental factors, which leads to the decrease of bone strength, makes the bone brittle, and raises the possibility of bone fracture. However, the exact mechanism that determines the progression of OP remains to be underlined. There are hundreds of trillions of symbiotic bacteria living in the human gut, which have a mutually beneficial symbiotic relationship with the human body that helps to maintain human health. With the development of modern high-throughput sequencing (HTS) platforms, there has been growing evidence that the gut microbiome may play an important role in the programming of bone metabolism. In the present review, we discuss the potential mechanisms of the gut microbiome in the development of OP, such as alterations of bone metabolism, bone mineral absorption, and immune regulation. The potential of gut microbiome-targeted strategies in the prevention and treatment of OP was also evaluated. Cite this article: Bone Joint Res 2020;9(8):524–530.

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Osteoporosis: From Molecular Mechanisms to Therapies

Cited by 15 publications

References 16 publications

Synovial Fluid Interleukin-16 Contributes to Osteoclast Activation and Bone Loss through the JNK/NFATc1 Signaling Cascade in Patients with Periprosthetic Joint Infection

Synovial Fluid Interleukin-16 Contributes to Osteoclast Activation and Bone Loss through the JNK/NFATc1 Signaling Cascade in Patients with Periprosthetic Joint Infection

Long non-coding RNA MIR22HG promotes osteogenic differentiation of bone marrow mesenchymal stem cells via PTEN/ AKT pathway

Gut microbiome and osteoporosis

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