Jesse E. Otero

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Monocytes differentiate into osteoclasts through stimulation of receptor activator of NF-kappaB (RANK). Many downstream effectors of RANK play a positive role in osteoclastogenesis, but their relative importance in osteoclast differentiation is unclear. We report the discovery that activation of a single pathway downstream of RANK is sufficient for(More)
Generalized arterial calcification (AC) of infancy (GACI) is an autosomal recessive disorder that features hydroxyapatite deposition within arterial elastic fibers. Untreated, approximately 85% of GACI patients die by 6 months of age from cardiac ischemia and congestive heart failure. The first-generation bisphosphonate etidronate (EHDP;(More)
Physiologic osteoclastogenesis entails activation of multiple signal transduction pathways distal to the cell membrane receptor RANK. However, atypical osteoclastogenesis driven by pro-inflammatory stimuli has been described. We have reported recently a novel mechanism whereby endogenous mutational activation of the classical NF-kB pathway is sufficient to(More)
Chronic recurrent multifocal osteomyelitis (CRMO) is a human autoinflammatory disorder that primarily affects bone. Missense mutation (L98P) of proline-serine-threonine phosphatase-interacting protein 2 (Pstpip2) in mice leads to a disease that is phenotypically similar to CRMO called chronic multifocal osteomyelitis (cmo). Here we show that deficiency of(More)
Particle-induced periprosthetic osteolysis is the major cause for orthopedic implant failure. This failure is mediated mainly by the action of osteoclasts, the principal cells responsible for bone resorption and osteolysis. Therapeutic interventions to alleviate osteolysis have been focused on understanding and targeting mechanisms of osteoclastogenesis.(More)
It has been reported previously that inhibitory kappaB kinase (IKK) supports osteoclastogenesis through NF-kappaB-mediated prevention of apoptosis. This finding suggests that the ligand for receptor activator of NF-kappaB (RANKL), the master osteoclastogenic cytokine, induces apoptosis of osteoclast precursors (OCPs) in the absence of IKKbeta/NF-kappaB(More)
NF-kappaB is a vital component of the molecular programs for immune cell development and activation, inflammatory responses, and osteoclast differentiation. This transcriptional regulatory family is activated by diverse immunological and inflammatory stimuli and contributes to both positive feedback of the immune and osteolytic responses as well as their(More)
Physiologic osteoclastogenesis entails activation of multiple signal transduction pathways distal to the cell membrane receptor RANK. However, atypical osteoclastogenesis driven by pro-inflammatory stimuli has been described. We have reported recently a novel mechanism whereby endogenous mutational activation of the classical NF-κB pathway is sufficient to(More)
The transcription factor NF-kappaB is crucial for numerous cellular functions such as survival, differentiation, immunity, and inflammation. A key function of this family of transcription factors is regulation of osteoclast differentiation and function, which in turn controls skeletal homeostasis. The IkappaB kinase (IKK) complex, which contains IKKalpha,(More)
The transcription factor NF-kappaB is essential for osteoclastogenesis and is considered an immune-modulator of rheumatoid arthritis and inflammatory osteolysis. Activation of NF-kappaB subunits is regulated by the upstream IkappaB kinase (IKK) complex which contains IKKalpha, IKKbeta, and IKKgamma; the latter also known as NF-kappaB essential modulator(More)