Biomedical subjects

Jeffrey Luo

Publications and source records attributed to Jeffrey Luo.

6 recordsLinked to original sources

PubMed2006

Kienböck's disease: an approach to treatment.

Since its description in 1910, Kienböck's disease has continued to be a difficult problem for clinicians as well as patients. An incomplete understanding of the etiology as well as the natural history of the disease has led to an assortment of surgical treatment options. The authors present a review of Kienböck's disease and the theories behind different surgical interventions, as well as their current approach to treatment of patients with Kienböck's disease.

Algorithms↗

PubMed2005

The future of flexor tendon surgery.

Clinical outcomes following flexor tendon repair have made significant improvements in the last 50 years. In that time standard treatment has evolved from secondary grafting to primary repair with postoperative rehabilitation protocols. Unfortunately, excellent results are not yet attained universally following treatment. Improving understanding of tendon healing at the cellular, molecular, and genetic levels will likely enable surgeons to modulate the normal repair process. We now look toward biologic augmentation of flexor tendon repairs to address the problems of increasing tensile strength while reducing adhesion formation following injury and operative repair.

Genetic Therapy↗

PubMed2005

Characterization of adenovirus-mediated gene transfer in rabbit flexor tendons.

PURPOSE: Adenoviral vector-based gene therapy is a promising technique for the delivery of growth factors to tendons. The objective of this study was to determine whether rabbit flexor tendons could be transduced effectively by adenoviral vectors and whether the introduction of adenoviral vectors would cause a notable local inflammatory response. METHODS: Recombinant adenoviruses expressing green fluorescent protein (AdGFP) or BMP-13 (AdBMP-13) were constructed and 3 different viral titers (1 x 10(7), 1 x 10(8), and 1 x 10(9)) were tested in this study. The second through fifth tendons of the forepaws and hindpaws of a New Zealand white rabbit were identified surgically and injected with different viral titers of adenoviruses. The fifth tendon was used as a control. The tendons were harvested 12 days after surgery. The retrieved tendons were sectioned to measure transgene expression, as well as for histologic evaluation. RESULTS: At all tested viral titers an efficient dose-dependent transgene expression was detected in all samples at 12 days after injection. At the highest dose the injection sites were notable for lymphocytic infiltration, suggesting that injected adenoviral vectors can illicit some local inflammatory response. Lymphocytic infiltration was much less apparent, however, in the tendons injected with lower titers of adenoviral vectors. There was no evidence of a massive inflammatory response and/or cell death. CONCLUSIONS: Our findings show that adenovirus-based gene therapy is an efficient means of gene delivery to rabbit flexor tendons. Transduction efficiency of transgenes was dose dependent across the tested titers, although adenovirus-induced inflammation was notable only at the highest titer. This indicates that efficient gene transfer without notable local inflammatory response may be achieved by using the lower titers. Although adenovirus-induced inflammation can be minimized by using lower viral titers, its impact on adhesion formation in the long term remains unknown.

Adenoviridae↗

PubMed2005

Gene therapy for bone regeneration.

Efficacious bone regeneration could revolutionize the clinical management of many bone and musculoskeletal disorders. Bone has the unique ability to regenerate and continuously remodel itself throughout life. However, clinical situations arise when bone is unable to heal itself, as with segmental bone loss, fracture non-union, and failed spinal fusion. This leads to significant morbidity and mortality. Current attempts at improved bone healing have been met with limited success, fueling the development of improved techniques. Gene therapy in many ways represents an ideal approach for augmenting bone regeneration. Gene therapy allows specific gene products to be delivered to a precise anatomic location. In addition, the level of transgene expression as well as the duration of expression can be regulated with current techniques. For bone regeneration, the gene of interest should be delivered to the fracture site, expressed at appropriate levels, and then deactivated once the fracture has healed. Delivery of biological factors, mostly bone morphogenetic proteins (BMPs), has yielded promising results both in animal and clinical studies. There has also been tremendous work on discovering new growth factors and exploring previously defined ones. Finally, significant advances are being made in the delivery systems of the genes, ranging from viral and non-viral vectors to tissue engineering scaffolds. Despite some public hesitation to gene therapy, its use has great potential to expand our ability to treat a variety of human bone and musculoskeletal disorders. It is conceivable that in the near future gene therapy can be utilized to induce bone formation in virtually any region of the body in a minimally invasive manner. As bone biology and gene therapy research progresses, the goal of successful human gene transfer for augmentation of bone regeneration draws nearer.

Animals↗

PubMed2004

Connective tissue growth factor (CTGF) is regulated by Wnt and bone morphogenetic proteins signaling in osteoblast differentiation of mesenchymal stem cells.

Osteoblast lineage-specific differentiation of mesenchymal stem cells is a well regulated but poorly understood process. Both bone morphogenetic proteins (BMPs) and Wnt signaling are implicated in regulating osteoblast differentiation and bone formation. Here we analyzed the expression profiles of mesenchymal stem cells stimulated with Wnt3A and osteogenic BMPs, and we identified connective tissue growth factor (CTGF) as a potential target of Wnt and BMP signaling. We confirmed the microarray results, and we demonstrated that CTGF was up-regulated at the early stage of BMP-9 and Wnt3A stimulations and that Wnt3A-regulated CTGF expression was beta-catenin-dependent. RNA interference-mediated knockdown of CTGF expression significantly diminished BMP-9-induced, but not Wnt3A-induced, osteogenic differentiation, suggesting that Wnt3A may also regulate osteoblast differentiation in a CTGF-independent fashion. However, constitutive expression of CTGF was shown to inhibit both BMP-9- and Wnt3A-induced osteogenic differentiation. Exogenous expression of CTGF was shown to promote cell migration and recruitment of mesenchymal stem cells. Our findings demonstrate that CTGF is up-regulated by Wnt3A and BMP-9 at the early stage of osteogenic differentiation, which may regulate the proliferation and recruitment of osteoprogenitor cells; however, CTGF is down-regulated as the differentiation potential of committed pre-osteoblasts increases, strongly suggesting that tight regulation of CTGF expression may be essential for normal osteoblast differentiation of mesenchymal stem cells.

Adenoviridae↗

PubMed2004

Inhibitor of DNA binding/differentiation helix-loop-helix proteins mediate bone morphogenetic protein-induced osteoblast differentiation of mesenchymal stem cells.

Bone morphogenetic proteins (BMPs) belong to the TGF-beta superfamily and play an important role in development and in many cellular processes. We have found that BMP-2, BMP-6, and BMP-9 induce the most potent osteogenic differentiation of mesenchymal stem cells. Expression profiling analysis has revealed that the Inhibitors of DNA binding/differentiation (Id)-1, Id-2, and Id-3 are among the most significantly up-regulated genes upon BMP-2, BMP-6, or BMP-9 stimulation. Here, we sought to determine the functional role of these Id proteins in BMP-induced osteoblast differentiation. We demonstrated that the expression of Id-1, Id-2, and Id-3 genes was significantly induced at the early stage of BMP-9 stimulation and returned to basal levels at 3 days after stimulation. RNA interference-mediated knockdown of Id expression significantly diminished the BMP-9-induced osteogenic differentiation of mesenchymal progenitor cells. Surprisingly, a constitutive overexpression of these Id genes also inhibited osteoblast differentiation initiated by BMP-9. Furthermore, we demonstrated that BMP-9-regulated Id expression is Smad4-dependent. Overexpression of the three Id genes was shown to promote cell proliferation that was coupled with an inhibition of osteogenic differentiation. Thus, our findings suggest that the Id helix-loop-helix proteins may play an important role in promoting the proliferation of early osteoblast progenitor cells and that Id expression must be down-regulated during the terminal differentiation of committed osteoblasts, suggesting that a balanced regulation of Id expression may be critical to BMP-induced osteoblast lineage-specific differentiation of mesenchymal stem cells.

Adenoviridae↗