Faculty Bibliography

The effects of BMP2 on bone marrow stromal cell differentiation and bone formation after bone marrow ablation were determined using C57 BL/6J (B6) mice. Inhibition of BMP2 expression with lentiviral BMP2 shRNA prevented both mineralized nodule formation in vitro and bone formation in vivo, and blocked the expression of Runx2 and osterix, transcriptional determinants of terminal osteogenic differentiation. No effect was observed on the expression of Sox9, a transcription factor, which is the one of the first transcriptional determinant to be expressed in committed chondroprogenitor and osteoprogenitor cells. In vitro studies showed that exogenously added BMP7 rescued the expression of osterix and enhanced the expression of Sox9, but had no effect on the expression of Runx2, while it only partially recovered the development of mineral deposition in the cultures. On the other hand, the exogenous addition of BMP2 rescued both Runx2 and osterix expression, did not enhance the expression of Sox9, but fully recovered the inhibition of mineral deposition in the cultures. Using antibodies against CD146 and Sox9, immunohistological examination of the cell populations found in the medullary space three days after bone marrow ablation, showed qualitatively equal numbers of cells expressing these skeletal progenitor and stem cell markers in control and BMP2 shRNA treated animals. Fluorescence Activated Cell Sorting (FACS) analysis of the cells found with the marrow cavities at three days after marrow ablation using CD146 antibody showed near equal numbers of immunopositive cells in both control and shRNA treated animals. In summary, the differences observed in vitro for BMP2 and BMP7 on osteogenic gene expression and mineralization suggest that they have differing effects on bone cell differentiation. These results further demonstrate that in vivo BMP2 is a central morphogenetic regulator of post natal osteoprogenitor differentiation, but does not affect recruitment of progenitors to the osteoblastic lineage.

BACKGROUND: Chronic plantar heel pain (CPHP) is common and is thought to have a detrimental impact on health-related quality of life. However, no study has used normative data or a control data set for comparison of scores. Therefore, we describe the impact of CPHP on foot-specific and general health-related quality of life by comparing CPHP subjects with controls. METHODS: Foot Health Status Questionnaire scores were compared in 80 subjects with CPHP and 80 sex- and age-matched controls without CPHP. RESULTS: The CPHP group demonstrated significantly poorer foot-specific quality of life, as evidenced by lower scores on the foot pain, foot function, footwear, and general foot health domains of the Foot Health Status Questionnaire. The group also demonstrated significantly poorer general health-related quality of life, with lower scores on the physical activity, social capacity, and vigor domains. In multivariate analysis, CPHP remained significantly and independently associated with Foot Health Status Questionnaire scores after adjustment for differences in body mass index. Age, sex, body mass index, and whether symptoms were unilateral or bilateral had no association with the degree of impairment in people with CPHP. CONCLUSION: Chronic plantar heel pain has a significant negative impact on foot-specific and general health-related quality of life. The degree of negative impact does not seem to be associated with age, sex, or body mass index

BACKGROUND: Chronic plantar heel pain (CPHP) is one of the most common musculoskeletal disorders of the foot, yet its aetiology is poorly understood. The purpose of this study was to examine the association between CPHP and a number of commonly hypothesised causative factors. METHODS: Eighty participants with CPHP (33 males, 47 females, mean age 52.3 years, S.D. 11.7) were matched by age (+/- 2 years) and sex to 80 control participants (33 males, 47 females, mean age 51.9 years, S.D. 11.8). The two groups were then compared on body mass index (BMI), foot posture as measured by the Foot Posture Index (FPI), ankle dorsiflexion range of motion (ROM) as measured by the Dorsiflexion Lunge Test, occupational lower limb stress using the Occupational Rating Scale and calf endurance using the Standing Heel Rise Test. RESULTS: Univariate analysis demonstrated that the CPHP group had significantly greater BMI (29.8 +/- 5.4 kg/m2 vs. 27.5 +/- 4.9 kg/m2; P < 0.01), a more pronated foot posture (FPI score 2.4 +/- 3.3 vs. 1.1 +/- 2.3; P < 0.01) and greater ankle dorsiflexion ROM (45.1 +/- 7.1 degrees vs. 40.5 +/- 6.6 degrees; P < 0.01) than the control group. No difference was identified between the groups for calf endurance or time spent sitting, standing, walking on uneven ground, squatting, climbing or lifting. Multivariate logistic regression revealed that those with CPHP were more likely to be obese (BMI > or = 30 kg/m2) (OR 2.9, 95% CI 1.4 - 6.1, P < 0.01) and to have a pronated foot posture (FPI > or = 4) (OR 3.7, 95% CI 1.6 - 8.7, P < 0.01). CONCLUSION: Obesity and pronated foot posture are associated with CPHP and may be risk factors for the development of the condition. Decreased ankle dorsiflexion, calf endurance and occupational lower limb stress may not play a role in CPHP

OBJECTIVES: To investigate the efficacy of a topical wheatgrass cream for improving pain and function in patients with chronic plantar fasciitis. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Eighty participants with chronic plantar fasciitis were randomly assigned to a treatment group (wheatgrass cream) or a control group (placebo cream). All participants applied a cream twice daily for 6 weeks. Follow up was conducted at 6 and 12 weeks. MAIN OUTCOME MEASURES: Visual Analogue Scale (VAS) for daily first-step pain and the Foot Health Status Questionnaire (FHSQ) for overall foot function. Secondary measures of foot posture, calf muscle strength and range of ankle dorsiflexion were also assessed. RESULTS: No significant differences were found between groups with respect to main outcomes of first-step pain or foot function at any time. Both groups improved significantly from baseline to 6 weeks, and these improvements were maintained at 12 weeks. CONCLUSIONS: The topical application of wheatgrass cream is no more effective than a placebo cream for the treatment of chronic plantar fasciitis

Various visual cues provide information about depth and shape in a scene. When several of these cues are simultaneously available in a single location in the scene, the visual system attempts to combine them. In this paper, we discuss three key issues relevant to the experimental analysis of depth cue combination in human vision: cue promotion, dynamic weighting of cues, and robustness of cue combination. We review recent psychophysical studies of human depth cue combination in light of these issues. We organize the discussion and review as the development of a model of the depth cue combination process termed modified weak fusion (MWF). We relate the MWF framework to Bayesian theories of cue combination. We argue that the MWF model is consistent with previous experimental results and is a parsimonious summary of these results. While the MWF model is motivated by normative considerations, it is primarily intended to guide experimental analysis of depth cue combination in human vision. We describe experimental methods, analogous to perturbation analysis, that permit us to analyze depth cue combination in novel ways. In particular these methods allow us to investigate the key issues we have raised. We summarize recent experimental tests of the MWF framework that use these methods.