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1.  Measuring intranodal pressure and lymph viscosity to elucidate mechanisms of arthritic flare and therapeutic outcomes 
Rheumatoid arthritis (RA) is a chronic autoimmune disease with episodic flares in affected joints, whose etiology is largely unknown. Recent studies in mice demonstrated alterations in lymphatics from affected joints precede flares. Thus, we aimed to develop novel methods for measuring lymph node pressure and lymph viscosity in limbs of mice. Pressure measurements were performed by inserting a glass micropipette connected to a pressure transducer into popliteal lymph nodes (PLN) or axillary lymph nodes (ALN) of mice and determined that the lymphatic pressures were 9 and 12 cm of water, respectively. We are also developing methods for measuring lymph viscosity in lymphatic vessels afferent to PLN, which can be measured by multi-photon fluorescence recovery after photobleaching (MP-FRAP) of FITC-BSA injected into the hind footpad. These results demonstrate the potential of lymph node pressure and lymph viscosity measurements, and warrant future studies to test these outcomes as biomarkers of arthritic flare.
PMCID: PMC3334848  PMID: 22172039
Rheumatoid Arthritis; Lymph Node; Flare; Lymphatic Pressure; Lymph Viscosity
2.  Effects of anti-resorptive agents on osteomyelitis: Novel insights on osteonecrosis of the jaw (ONJ) pathogenesis 
The effects of anti-resorptive agents (i.e. alendronate (Aln), osteoprotegerin (OPG)) on bone infection are unknown. Thus, their effects on implant-associated osteomyelitis (OM) were investigated in mice using PBS (placebo), gentamycin and etanercept (TNFR:Fc) controls. None of the drugs affected humoral immunity, angiogenesis, or chronic infection. However, the significant (p<0.05 vs. PBS) inhibition of cortical osteolysis and decreased draining lymph node size in Aln and OPG treated mice was associated with a significant (p<0.05) increase in the incidence of high-grade infections during the establishment of OM. In contrast, the high-grade infections in TNFR:Fc treated mice were associated with immunosuppression, as evidenced by the absence of granulomas and presence of Gram+ biofilm in the bone marrow. Collectively, these findings indicate that while anti-resorptive agents do not exacerbate chronic OM, they can increase the bacterial load during early infection by decreasing lymphatic drainage and preventing the removal of necrotic bone that harbors the bacteria.
PMCID: PMC2947350  PMID: 20392222
3.  Functions of NF-κB in Bone 
NF-κB is a set of multifunctional transcriptional factors that regulate expression of genes involved in numerous normal cellular activities. They also are activated in many inflammatory and neoplastic conditions in which their expression may be stimulated by pro-inflammatory cytokines. NF-κB in turn, regulates the expression of cytokines and so can mediate autocrine, self-amplifying cycles of cytokine release and NF-κB activation leading to maintenance of inflammatory reactions beyond the initial stimulus, as seen in rheumatoid arthritis and asthma. Since discovery of the requirement of NF-κB for basal and cytokine-induced osteoclast formation in the mid-1990s, much has been learned about the role of NF-κB in bone. NF-κB has roles in skeletal development, endochondral ossification, osteoclast and osteoblast functions, and common bone diseases. NF-κB inhibitors have been developed, but none has made it to clinical trials for the treatment of common bone diseases. Here we review the roles for NF-κB in bone and in common bone diseases.
PMCID: PMC3013362  PMID: 20392262

Results 1-3 (3)