The Extracellular Signal-Regulated Kinase Mitogen-Activated Protein Kinase Pathway in Osteoblasts

Extracellular signal-regulated kinases (ERKs) are evolutionarily ancient signal transducers of the mitogen-activated protein kinase (MAPK) family that have long been linked to the regulation of osteoblast differentiation and bone formation. Here, we review the physiological functions, biochemistry, upstream activators, and downstream substrates of the ERK pathway. ERK is activated in skeletal progenitors and regulates osteoblast differentiation and skeletal mineralization, with ERK serving as a key regulator of Runt-related transcription factor 2, a critical transcription factor for osteoblast differentiation. However, new evidence highlights context-dependent changes in ERK MAPK pathway wiring and function, indicating a broader set of physiological roles associated with changes in ERK pathway components or substrates. Consistent with this importance, several human skeletal dysplasias are associated with dysregulation of the ERK MAPK pathway, including neurofibromatosis type 1 and Noonan syndrome. The continually broadening array of drugs targeting the ERK pathway for the treatment of cancer and other disorders makes it increasingly important to understand how interference with this pathway impacts bone metabolism, highlighting the importance of mouse studies to model the role of the ERK MAPK pathway in bone formation.

Osteoimmunology: A Brief Introduction

Recent investigations have demonstrated extensive reciprocal interactions between the immune and skeletal systems, resulting in the establishment of osteoimmunology as a cross-disciplinary field. Here we highlight core concepts and recent advances in this emerging area of study.

Functions of Ich-1(L). and Ich-1(S) in Apoptotic Signaling Pathway of jurkat T Cells / 대한면역학회지

Human caspase-2, Ich-1 (Ice and Ced-3 homolog), has two different forms of mRNA species derived from alternative splicing, which encodes Ich-1 and Ich-1s. Ich-1v which induces apoptosis is antagonist of Ich-1s which suppresses Rat-1 cell death by serum deprivation. To investigate functions of Ich-1 and Ich-1s in T celi apoptosis, the fusion DNA constructs were made with the ecto and transmembrane of CDB and Ich-lv or Ich-1s and CDS-Ich-1 or CD8-Ich-1s chimeric protein was transiently expressed on Jurkat T cells. Tyrosine phosphorylation of intracellular proteins was induced in these transfectans when activated shortly by anti-CDB Ab. CDB-Ich-li transfectant in serum-rich condition and CDB-Ich-ls transfectant in serum-deprived condition underwent apoptosis when treated with anti-CDS Ab or incubated with NIH3T3 cells expressing stably Fas-L on their surface. We also made six antisense DNA constructs which could specifically inhibit the expression of Ich-1v, Ich- 1s, and then they were transiently transfected into Jurkat T cell. The overexpression of both of the antisese- Ich-1 against N-terminal 42 bp and against C-terminal 366 bp inhibited apoptosis through Fas signalling. But, when three different forms of antisense-Ich-1s were overexpressed in their transfectants, antisense-DNA against N-terminal 197 bp increased knd the one against C-terminal 66 bp inhibited apoptosis, instead the full size of antisense-DNA did not give any effects on apoptosis through Fas pathway.

Supplement of Incomplete Apoptosis Through CD8/Fas Chimeric Molecule by PMA of IFN-gamma / 대한면역학회지

No abstract available.