Biomedical subjects

M L Olmedo

Publications and source records attributed to M L Olmedo.

4 recordsLinked to original sources

PubMed2000

Programmed cell death in post-traumatic bone callus.

Some osteoblasts in the expanded population of periosteal cells that occurs following bone injury are removed from the callus by apoptosis. Our objective was to study whether the consequences of activation of the death program could include feedback control of the healing response. Transforming growth factor beta and interleukin-1beta were delivered together continuously to a standardized tibial defect in rats for 3 days using implanted micro-osmotic pumps. The bones were recovered at 1, 2, 3, 5, 7, 10 and 14 days after injury (n = 6 in each treated and control group) and concentrations of proliferating cells, osteoblasts and apoptotic bodies were determined. The injury-induced apoptotic component of the healing response was shifted in time due to the combined cytokines, compared with vehicle only, with the result that the peak in the concentration of apoptotic bodies occurred 2-3 days earlier in the treated animals. Neither osteoprogenitor proliferation nor osteoblast concentration was affected by addition of the cytokines. The results suggested that activation of apoptosis during injury repair was not necessarily a passive consequence of the cellular response to injury. Programmed cell death could therefore have an active role in modulating bone repair.

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PubMed1995

Growth factor modulation of the formation of a molded vascularized bone graft in vivo.

Peptide growth factors are potent regulators of osteoblast differentiation, proliferation, and maturation. Two of these growth factors, transforming growth factor beta (TGF-beta) and basic fibroblast growth factor (bFGF), were used in an attempt to stimulate osteoneogenesis and angiogenesis in a molded vascularized bone graft in the rat. Custom chambers containing cancellous autograft bone and agarose beads and incubated with TGF-beta, bFGF, or a control solution, were closed around the femoral artery/vein pedicle for 2-4 weeks. Control grafts were completely necrotic and without mechanical integrity. TGF-beta grafts demonstrated active osteogenesis around necrotic bone, osteoclastic activity, and limited angiogenesis. Basic FGF grafts demonstrated substantial angiogenesis with limited osteoblastic activity. This study suggests that TGF-beta and bFGF stimulate populations of cells in the formation of a molded vascularized bone graft. TGF-beta induces the proliferation and/or activity of osteoblastic cells, while bFGF stimulates cells involved in angiogenesis. Despite these findings, an insoluble demineralized matrix component may be required for complete transformation and graft consolidation.

Animals↗

PubMed1994

An experimental rat model allowing controlled delivery of substances to evaluate fracture healing.

We present a method to study the in vivo delivery of any substance in a rat femur fracture model that allows precise administration with control of both substance dosage and temporal application in a reproducible and predictable manner. This method is easy to perform, requires no expensive materials, and provides the benefit of internal stabilization of the femur fracture. In this model, all wounds are closed after surgery with no external ports or catheters, significantly reducing the infection rate and the risk of dislodgement due to animal intervention. This model allows the study of different substances given at different times in the same animal, providing the potential to improve our understanding of the interactions of various substances on normal fracture healing.

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PubMedDate not supplied

Regulation of osteoblast levels during bone healing.

OBJECTIVE: To confirm the occurrence of programmed cell death of osteoblasts during bone healing and to evaluate the role of interleukin-1beta (IL-1beta) in regulating osteoblast concentration. STUDY DESIGN: Electron microscopic study of the response of rats to a controlled bone injury, and a randomized controlled study of the effect of IL-1beta administered continuously for three days. METHODS: A standardized defect (1.1 millimeter in diameter, 0.5 millimeter deep) was created unilaterally on the anteromedial surface of the tibia. In some animals, the injury site was recovered five days after operation and processed for ultrastructural evaluation of osteoblasts in the callus. In another group, IL-1beta was delivered to the bone defect using micro-osmotic pumps (0.5 nanograms/hour); control rats received vehicle only. The bones were recovered one to fourteen days after injury, and concentrations of proliferating cells, osteoblasts, and apoptotic bodies were determined. The amount of callus that formed in the defect was measured. RESULTS: Osteoblasts in the callus exhibited ultrastructural changes characteristic of cells undergoing apoptosis, including condensation of chromatin, membrane blebbing, formation of apoptotic bodies, and phagocytosis by nearby osteoblasts. Addition of IL-1beta significantly increased the number of osteoblasts at the injury site and significantly decreased the number of apoptotic bodies in relation to the number of osteoblasts. The amount of callus in the bone defect was not affected by IL-1beta treatment. CONCLUSION: The role of programmed cell death of osteoblasts as a normal concomitant of bone healing was confirmed. Evidence was found suggesting that IL-1beta mediated the appearance and disappearance of osteoblasts, possibly by affecting the rates of differentiation and apoptosis, respectively. Understanding these mechanisms conceivably could lead to the ability to control osteoblast levels at an injury site.

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