Bone Biology Week in Review: April 4 to April 8, 2011

Mustafa Ramazanoglu and colleagues, publishing in Clinical Oral Implants Research, observe that growth factors alone may not be enough to create stable osseointegration in biomimetic implants. This group looked at the performance of combined BMP and VEGF loaded biomaterial implants and concluded that while BMP+VEGF significantly increases bone volume density, it does not significantly increase bone to implant contact surface. This lead them to conclude "changes in the surface characteristics should be considered when designing growth factor-delivering surfaces."

Cornelius Von Wilmowsky and colleagues, publishing in Clinical Oral Implants Research, established a novel streptozotocin (STZ)  induced domestic pig model of diabetes mellitus. They went on to characterize changes in hard and soft tissues over a 12 month period. They conclude that an STZ dosage of 90 mg/kg body weight in the domestic pig is suitable for the induction of apparent diabetes with changes in soft and hard tissue apparent in as little as 6 months.

Keyung-Jo Seul and colleagues, publishing in Journal of Bone and Mineral Research, continue their work on MEF, the Myeloid elf-1-like factor. They have produced a transgenic mouse model which overexpresses MEF in osteoblasts under the control of the 2.3-kb Col1α1 promoter, named Col1α1-MEF. They report compromised femoral bone structure including low bone mass, few trabeculae, and thinner cortical walls. Investigating the cellular mechanisms of this change, they report large reductions in BFR, on the order of 40% as well as an increased number of ostoclasts. They conclude then that MEF appears to suppress bone formation in osteoblasts and indirectly stimulate osteoclast formation.

Alero F. Inyang and colleagues, publishing in Journal of Craniofacial Surgery, continue their work on mandibular distraction osteogenesis. Bone collected from the mandibular distraction sites could be used to replace bone lost cancer metastasis, particular in the head and  neck. They had previously shown in the rat mandible a reduction of bone density and mechanical strength following 36-Gy radiation therapy. Their present work investigates the parallel cellular changes. They observed significantly more osteoid (non-mineralized bone) in radiation dosed rats, suggesting either a reduction in osteoblast number or impared osteoblast function. Interestingly, they also report a loss of osteocytes as evidenced by a greater number of empty osteocyte lacunae. This loss of osteocytes raises the concern that a key signaling system in the onset of fracture repair may be compromised. They propose future work with anabolic agents to see if the effect of radiation therapy can be mitigated.

Li Laine Ooi and colleagues, publishing in Bone, continue their work with vitamin D deficiency in breast cancer metastasis to bone. In this project, they consider the effects on vitamin D deficiency in a mouse model of intra-skeletal breast cancer. In vitro treatment of MCF-7 breast cancer cells with vitamin D inhibited cell proliferation and increased apoptosis. In vivo, vitamin D deficient mice showed around a 50% increase in tumor area compared to vitamin D sufficient mice. Additionally, treatment with osteoprotegerin (an osteoclast inhibitor) reduced tumor burden by more than 90% in both vitamin D deficient and sufficient mice. Consequently, they suggest that tumor growth in this model is dependent on bone resorption and is exacerbated by a loss of vitamin D's ability to inhibit cell proliferation.