Blaine Christiansen, PhD

Contact Information

Email: bchristiansen@ucdavis.edu

Office Number: 916-734-3974

· Armaun Emami, Biomedical Engineering Graduate Student (Ph.D.), 2013-present
· Allison Hsia, Biomedical Engineering Graduate Student (Ph.D.), 2014-present
· Hailey Cunningham, Biomedical Engineering Graduate Student (Ph.D.), 2014-present

· Mollie Heffner, Biomedical Engineering Graduate Student (Ph.D.), 2011-2016
· Kevin Lockwood, M.S., Biomedical Engineering Graduate Student, 2012-2013, Current position: Research & Development Engineer- Ortho Development, Salt Lake City, UT
· Patrick Satkunananthan, M.S., Biomedical Engineering Graduate Student, 2012-2013, Current position: Process Engineer, Lumina, San Diego, CA
· Mohammad Khorasani, M.S., Biomedical Engineering Graduate Student, 2012-2013, Current position: Research & Development Engineer, Skeletal Kinetics LLC, Cupertino, CA
· Fengdong Zhao – Research Fellow. Current position: Professor, Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University.
· Sindi Diko, B.S., Post-Baccalaureate Fellow, 2012-2014, Current position: D.O. Student, Rocky Vista University College of Osteopathic Medicine.
· Matthew Anderson – Research Fellow. Current position: Medical Student, Albany Medical College, Albany, NY.
· Bryce Chu, B.S., Undergraduate Research Assistant, 2012-2013, Current position: D.O. Student, Touro College of Osteopathic Medicine
· Gregory Yeh, B.S., Undergraduate Research Assistant, 2011-2012, Current position: Associate Mechanical Engineer, Accel Biotech, Inc., Redwood City, CA
· Anisha Gaitonde, Undergraduate Research Assistant, 2014-2015
· Franklin Tarke, Undergraduate Research Assistant, 2015
· Joseph Pevec, Undergraduate Research Assistant, 2015
· Earl Lagmay, Undergraduate Research Assistant, 2015

2009- Member, Orthopaedic Research Society
2010- Member, American Society for Bone and Mineral Research
2012- Member, Osteoarthritis Research Society International
2014- Member, Journal of Orthopaedic Research Editorial Board

2005 ASME Summer Bioengineering Conference, 1st Place- Student Paper Competition
2010 American Society for Bone and Mineral Research, Young Investigator Award
2010 United States Bone and Joint Decade – Young Investigators Initiative
2011 American Society for Bone and Mineral Research Harold M. Frost Young Investigator Award
2014 International Bone and Mineral Society, Sun Valley Alice L. Jee Award
2014 American Society for Bone and Mineral Research, Junior Faculty Osteoporosis Research Award

Research Summary

The main focus of my research is adaption of musculoskeletal tissues to the mechanical environment, injury, aging, or disease. The musculoskeletal system has an innate ability to repair and optimize itself based on the mechanical demands placed on it. By studying this adaptation, we are able to uncover underlying mechanisms that contribute to diseases such as osteoporosis and osteoarthritis. My laboratory primarily utilizes small animal models, and quantifies adaptation using advanced imaging techniques, histology, and mechanical testing. I currently have several active areas of research, including investigation of mechanisms of post-traumatic osteoarthritis, studying the effect of peripheral sensory nerve activity in bone metabolism and adaptation, and investigation of systemic bone loss following a bone fracture or musculoskeletal injury. I describe these primary research areas in greater detail below.

I received my B.S. in Biological Systems Engineering from the University of Nebraska–Lincoln, and my M.S. and Ph.D. in Biomedical Engineering from Washington University in St. Louis. My doctoral research, under the direction of Professor Matthew J. Silva, studied the use of vibrational loading to initiate bone formation in mice. Low-magnitude vibrational loading has been proposed as a possible non-pharmacologic method of initiating bone formation or mitigating bone loss in elderly patients who may not be able to participate in a rigorous exercise program. I investigated the use of whole-body vibration to initiate bone formation, as well as the development and characterization of a novel method for vibrational loading of mice (constrained tibial vibration). This research involved in vivo mechanical loading of mice, quantification of bone microarchitecture using micro-computed tomography, analysis of bone formation using dynamic histomorphometry, harmonic vibration analysis using accelerometers, finite element analysis of bone mechanical loading, and strain gage analysis of bone deformation. The use of these techniques provided a rigorous training in musculoskeletal research of small animals from a biomechanical engineering perspective, and is translatable to other research questions involving skeletal adaptation. I was the first author of three scientific publications encompassing this research, and in 2005 I won 1st place in the Student Paper Competition at the American Society of Mechanical Engineers Summer Bioengineering Conference for my presentation “The effect of varying magnitudes of whole-body vibration on several skeletal sites in mice”.

After completing my doctoral research, I accepted a postdoctoral fellowship at Harvard Medical School, in the Center for Advanced Orthopedic Studies at Beth Israel Deaconess Medical Center, under the mentorship of Associate Professor Mary L. Bouxsein. The primary focus of my postdoctoral research was biomechanical mechanisms of vertebral fractures and spinal loading in humans. This research used quantitative computed tomography (QCT) scans of subjects from the Framingham Heart Study to construct subject-specific biomechanical models that could predict loads on the spine for various activities, combined with methods for estimating vertebral body strength in order to predict fracture risk. This research provided valuable experience in translational research, and further developed my expertise in biomechanical modeling of the musculoskeletal system. During my postdoctoral fellowship I co-authored seven publications, and in 2010 I was awarded a Young Investigator Award at the annual meeting of the American Society for Bone and Mineral Research for my presentation Contributions of cortical and trabecular bone to age-related declines in vertebral strength are not the same for men and women”.

As an Assistant Professor in the Department of Orthopaedics at UC Davis, I have continued my research in musculoskeletal adaptation. I currently have 24 publications that were produced during my time at UC Davis, including 10 as senior author. My current and ongoing research projects are detailed below:

Post-traumatic osteoarthritis (PTOA) is commonly a long-term consequence of traumatic joint injury, with approximately 50% of individuals with anterior cruciate ligament (ACL) rupture or meniscectomy developing PTOA within 10-20 years. Mechanisms of PTOA development include changes in the biomechanical stability and mechanical loading of the joint, injury-induced inflammation, and increased rates of subchondral bone and articular cartilage remodeling. However, the relative contributions of these mechanisms to PTOA development are not fully known. Surgical repair of ligaments in humans can effectively restore the biomechanical stability an injured joint, however these patients are still at an increased risk for developing PTOA, suggesting a mechanism that is not driven exclusively by biomechanical changes.

The long-term goal of this research is to determine the time course and mechanisms of PTOA progression, and investigate therapies that can be applied at the time of injury that will slow or prevent the onset of PTOA. In our lab we have developed a novel non-invasive mouse knee injury model that uses a single cycle of tibial compression overload to rupture the ACL, inducing inflammation and biomechanical changes in the joint. This injury method is a significant step forward for mouse models of PTOA, since it creates a joint injury response relevant to traumatic joint injury in humans. Other mouse models of PTOA initiate symptoms using various non-physiologic methods such as injection of collagenase, surgical transection of ligaments, or multiple bouts of mechanical loading, all of which fail to mimic clinically relevant injury conditions. Studies using our injury model have shown an increase in joint laxity after injury, significant and immediate inflammation, rapid and considerable remodeling of subchondral bone, and degeneration of articular cartilage.

Current status:

This mouse model was developed in my laboratory in collaboration with Dr. Dominik R. Haudenschild in the Department of Orthopaedics. We have spent the last several years characterizing this new model, and establishing the time course of bone and cartilage changes that occur following knee injury in mice. Our current work will further characterize the biomechanical factors contributing to musculoskeletal changes, quantify inflammation and early biological response following injury, and begin to investigate potential therapies aimed at preventing or slowing the onset of PTOA. I currently have seven senior author manuscripts based on this research. The first manuscript entitled “Musculoskeletal changes following non-invasive knee injury using a novel mouse model of post-traumatic osteoarthritis” was published in Osteoarthritis and Cartilage in 2012. This publication described the magnitude and time course of subchondral bone and articular cartilage degeneration following non-invasive injury in mice. A follow-up study entitled “Comparison of loading rate-dependent injury modes in a murine model of post-traumatic osteoarthritis” was published in the Journal of Orthopaedic Research in 2014. Subsequent studies include “In vivo fluorescence reflectance imaging to quantify sex-based differences in protease activity in a mouse model of post-traumatic osteoarthritis” and “Effect of alendronate on post-traumatic osteoarthritis induced by ACL rupture in mice”. I also recently published a review article entitled “Non-invasive mouse models of post-traumatic osteoarthritis”. This review describes the mouse model developed in my laboratory, along with other available non-invasive mouse models used by other groups. This review was co-authored by several preeminent investigators in the field of OA research, and will likely be an impactful summary of the current work in this area. In 2011 I won the ASBMR Harold M. Frost Young Investigator Award at the International Bone and Mineral Society Sun Valley Workshop for my presentation of this research.

Many risk factors for osteoporotic fracture risk have been identified, but one of the strongest predictors of a future fracture is a previous history of fracture at any skeletal site, even after controlling for bone mineral density. One possible explanation for this phenomenon is that a first (index) fracture is indicative of a pre-existing problem with bone quality. However, there is an intriguing alternative explanation: an index fracture may cause a systemic adaptive response that actively and permanently compromises the skeleton. This systemic reaction following fracture may include systemic inflammation, bone adaptation to mechanical disuse, vascular proliferation, and increased rates of bone remodeling. However, the systemic loss of bone following an initial fracture has not been quantified, and the specific mechanisms of this bone loss have not been identified.

Preliminary data from our lab indicate that bone fracture or musculoskeletal injury actively decreases trabecular bone volume at distant and unrelated skeletal sites. These data may partially explain why a previous history of fracture predicts future fracture risk in humans, and may have important implications for treatment. The long-term goal of this research is to investigate systemic loss of bone mass and strength following bone fracture, and to translate these findings to human health and treatment of clinical fractures.

Current status:

We are currently conducting research investigating systemic bone loss in mice as a result of femur fracture. We currently have one published manuscript describing the loss of trabecular bone at a distant skeletal site following non-invasive ACL injury in mice. This manuscript was published in a special issue of the Journal of Biomechanical Engineering with the theme of Trabecular Bone Mechanobiology. I also served as a guest editor for this special issue. We are currently working toward a large, comprehensive manuscript that will thoroughly describe this systemic bone loss response, including both young and aged mice. In 2014 I won the Junior Faculty Osteoporosis Research Award from the American Society for Bone and Mineral Research (ASBMR) for this research.

Considerable degeneration of peripheral sensory nerve tissue and function occurs with aging. It is likely that this loss of nerve function affects bone metabolism in aged subjects, as it has been extensively shown that neuropeptides can affect the function of osteoblasts and osteoclasts in vitro, and nerve deactivation causes bone loss in vivo. Despite strong evidence of a link between sensory nerve function and bone cells, the role of decreased sensory nerve function in bone metabolism and bone adaptation has not been investigated. This lack of knowledge is an important problem, because identifying mechanisms of age-related bone loss is a crucial first step holding back the development of treatments aimed at maintaining healthy bone turnover and preventing or slowing the loss of bone mass with age.

Our long-term goal is to establish the role of peripheral sensory nerve function on bone metabolism in vivo. Our current studies have used capsaicin-treated mice as a model of decreased peripheral sensory nerve function. Neonatal capsaicin treatment in mice activates the transient receptor potential cation channel subfamily V member 1 (TrpV1, also known as the capsaicin receptor or the vanilloid receptor 1), which is expressed by unmyelinated and small diameter myelinated sensory neurons, but not motor neurons, large diameter sensory neurons, or sympathetic neurons, therefore muscle activity (and subsequent mechanical loading of bone) is not disrupted.

Current status:

We have published a study investigating the effect of peripheral sensory nerve inactivation in skeletal development and basal bone metabolism, and have recently submitted a manuscript for a study investigating the effect of sensory nerve inactivation on bone adaptation to increased mechanical loading.