Adult stem cell treatments for diseases?
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Adult↗
Biomedical subjects
Steven Teitelbaum
Publications and source records attributed to Steven Teitelbaum.
Breast augmentation roundtable.
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Female↗
Soluble RANKL and risk of nontraumatic fracture.
CONTEXT: The receptor activator of nuclear factor kappaB ligand (RANKL) is essential for osteoclast and, possibly, osteoblast activation and may represent a key link between bone formation and resorption. OBJECTIVE: To determine the relationship between serum level of RANKL and the risk of nontraumatic fracture. DESIGN, SETTING, AND PARTICIPANTS: As part of a prospective population-based study conducted in Bruneck, Italy, we recorded all fractures that occurred between 1990 and 2000 in 906 participants and classified them as traumatic (n = 115) or nontraumatic (n = 31). Serum levels of RANKL and osteoprotegerin and characteristics of bone metabolism and lifestyle were assessed in 1990 and at follow-up in 1995 and 2000. MAIN OUTCOME MEASURE: Incident nontraumatic fracture by levels of RANKL. RESULTS: Levels of RANKL did not differ between sexes and were not related to age, menopausal status, lifestyle characteristics, or data from bone ultrasound at the heel. However, RANKL emerged as a significant predictor of nontraumatic fracture. In pooled logistic regression analysis, the relative risks of nontraumatic fracture in the lowest and middle vs highest tertile for RANKL were 10.0 (95% confidence interval [CI], 2.3-43.1) and 3.9 (95% CI, 0.8-19.0) (P<.001 for trend), respectively. Patients in the highest-tertile group had a low risk of fracture even in the presence of other predisposing factors, whereas women aged 60 years or older in the lowest tertile had a 5-year rate of nontraumatic fracture greater than 7%. CONCLUSIONS: A low level of RANKL is an independent predictor of nontraumatic fracture. This finding is consistent with the hypothesis of an important role of RANKL in human bone turnover and if confirmed in future investigations may gain relevance for assessment of fracture risk.
Aged↗
Tumor necrosis factor-alpha mediates polymethylmethacrylate particle-induced NF-kappaB activation in osteoclast precursor cells.
Tumor necrosis factor-alpha (TNF) is a potent osteoclastogenic cytokine that has a fundamental role in the pathogenesis of implant particle-induced osteolysis. The nuclear transcription factor NF-kappaB mediates TNF signaling and this transcription complex is necessary for osteoclastogenesis. Because polymethylmethacrylate (PMMA) particles cause osteolysis, we reasoned the PMMA would induce NF-kappaB activation. In fact, we find that exposure of osteoclast precursors, in the form of colony stimulating factor-1 (CSF-1) dependent murine bone marrow macrophages, to PMMA particles prompts nuclear translocation and activation of NF-kappaB. Supershift assays confirm the presence of the p50 and p65 NF-kappaB subunits in the activated transcription factor. Particle-induced NF-kappaB activation is equal in both wild type and LPS- hyporesponsive cells indicating that the phenomenon does not represent endotoxin contamination. A soluble, competitive inhibitor of TNF (huTNFr:Fc) dampens particle-directed NF-kappaB activation and this response is also abrogated in TNF-/- osteoclast precursors. Thus, PMMA particle activation of NF-kappaB is a secondary event resulting from enhanced TNF expression and is independent of LPS contamination.
Animals↗