Bone Biology and Disease
Our Bone Biology and Disease program is focused on defining the signals and mechanisms important for bone formation and resorption in both normal and pathological situations (osteoporosis and osteopetrosis). While it is known that osteoblasts differentiate and localize the formation of new bone to regions where osteoclastic bone resorption has occurred, the signals responsible for this coupling effect are unknown and have become a focus of this research program. Another major research area in this program is centered on the pathophysiology of bone erosions in inflammatory arthritis, wear debris-induced osteolysis, which is responsible for aseptic loosening of orthopaedic implants, and bone infections, or osteomyelitis. We have also made major advances in understanding how environmental hazards/toxins, such as lead and smoke, can predispose individuals to bone loss or osteoporosis.
Program Faculty: Cheryl Ackert-Bicknell, Brendan Boyce, Laura Calvi, Roman Eliseev, J. Edward Puzas, Edward M. Schwarz, Lianping Xing
Bone Cancer Biology
Bone is a common site of breast and prostate cancer metastasis. It is also a site for the formation of primary tumors. In our Bone Cancer Biology program, we are studying the mechanisms of bone destruction following breast and prostate cancer metastasis and the regulation of malignant progression. Additional fields of active study include investigations into the mechanisms of radiation therapy resistance that is exhibited by cartilage and tumor cells and the survival vs. apoptotic processes of primary bone tumor cells.
Program Faculty: J. Edward Puzas, Wakenda Tyler, Roman Eliseev
Cartilage Biology and Arthritis
Our Cartilage Biology and Arthritis program investigates the mechanisms of chondrogenesis, chondrocyte maturation, and chondrocyte metabolism during normal skeletal growth and cartilage disease. A major emphasis of this program is geared toward using genetic and injury induced animal models to uncover the pathologic processes associated with inflammatory and non-inflammatory arthritis including: rheumatoid arthritis, psoriatic arthritis, lupus arthritis, and osteoarthritis. Our belief is that combining laboratory research with clinical investigation is the most effective way to bring better treatments to people affected by all types of arthritic disease.
Program Faculty: Brendan Boyce, John Elfar, Jennifer Jonason, Amy Lerner, Robert Mooney, Christopher Ritchlin, Randy Rosier, Edward M. Schwarz, Lianping Xing, Xinping Zhang, Michael J. Zuscik
Sarcopenia is the accelerated loss of skeletal muscle mass, and function observed in most members of the elderly population, and is a significant contributor to falls, frailty and loss in functional mobility, disabilities related to sarcopenia are a burgeoning cost to the US healthcare system. Additionally, the progression of sarcopenia correlates with reductions in neuromuscular junctions (NMJs), and the number and function of resident stem cells of skeletal muscle (satellite cells, SCs), which are also critically involved in the repair of injured muscle. To further understand the role of satellite cells in sarcopenia, NMJ, and skeletal muscle repair, the CMSR has research programs that utilize targeted mouse genetics and injury models to determine how molecules of interest affect satellite cell fate, and skeletal muscle regenerative outcomes. We hope insights gained from these studies can be exploited to attenuate the exacerbation of comorbidities, and onset of disability associated with sarcopenia.
Program Faculty: Joe Chakkalakal, John Elfar, Robert Dirksen, Richard Moxley, Charles Thornton
Our Musculoskeletal Development program is focused on identifying the mechanisms that underlie multiple aspects of axial and appendicular skeletal and skeletal muscle development including: patterning events, chondrogenesis, myogenesis, endochondral and intramembranous bone development, and joint formation. Developmental studies using genetic mouse models and primary cell culture techniques have identified multiple signaling molecules and transcription factors that are not only critical for normal musculoskeletal development, but are also implicated in congenital pediatric musculoskeletal disorders and adult musculoskeletal diseases.
Program Faculty: Joe Chakkalakal, Jennifer Jonason, Catherine K. Kuo, James Sanders, Michael Zuscik
Musculoskeletal infection is the bane of orthopaedic surgery, and is associated with very poor clinical outcomes and crippling healthcare cost. To address this the CMSR has active research projects aimed at elucidating the natural history of Staphylococcus aureus bone infection and biofilm formation, the etiology of co-morbidities (i.e. obesity, diabetes, aging), and developing novel diagnostics and interventions. The breadth of this research spans proof of concept research performed in a murine osteomyelitis model, through IND enabling studies in a novel clinically relevant sheep model of 2-stage exchange of an infected tibial implant with monoclonal antibodies (mAb) produced by our trainees in our cGMP facility. Additional projects involve: the study of Type I and Type II diabetes in a murine osteomyelitis model; a world-wide Staphylococcal bone infection registry of serum and clinical isolates from 400 osteomyelitis patients; development of a custom 3D-printed antibiotic-impregnated calcium phosphate/collagen spacer evaluated in the murine osteomyelitis model; developed a 14-antigen Luminex assay as a serum diagnostic for S. aureus infection; and investigation of Staphylococcal biofilm formation on stainless steel and titanium implants in bone.
Program Faculty: Edward Schwarz, Hani Awad, John Daiss, Robert Mooney
Musculoskeletal Repair and Maintenance
In our Musculoskeletal Repair program, we perform translational studies designed to help understand common problems encountered by physicians when treating a wide array of musculoskeletal related injuries. Animal models of facture healing, structural bone grafting, distraction osteogenesis, skeletal muscle degeneration, skeletal muscle atrophy, and tendon injury have been developed to study repair mechanisms. Current applications of our animal models include: identifying mechanisms for enhanced musculoskeletal repair, devising cell-based tissue engineering, pharmacological and gene therapy approaches to enhance bone, tendon and skeletal muscle repair, regeneration or maintenance, and identifying cell-signaling pathways that control mesenchymal and skeletal muscle stem cell activation, expansion, and differentiation during bone, cartilage and skeletal muscle repair.
Click the video above to hear Dr. Xinping Zhang describe her newest project
"Identification of the Effective Vascular Progenitors for Bone Repair and Regeneration"
Program Faculty: Cheryl Ackert-Bicknell, Hani Awad, Danielle Benoit, Joe Chakkalakal, John Elfar, Catherine K. Kuo, Alayna Loiselle, Edward M. Schwarz, Xinping Zhang, Michael J. Zuscik
Musculoskeletal Stem Cell Biology
Our Musculoskeletal Stem Cell Biology program covers broad interests in the identification, self-renewal, maintenance, cell fate determination, and differentiation of several types of musculoskeletal stem cells. These include mesenchymal stem cells that give rise to cartilage, bone, fat, and connective tissues, hematopoietic stem cells that generate all blood cells and are housed in the bone marrow, and skeletal muscle stem cells that are required for skeletal muscle growth and regeneration. We study these stem cells both in the context of embryonic development and adult musculoskeletal repair and tissue engineering. We are attempting to gain a broader understanding of the molecular circuits that regulate stem cell self-renewal and differentiation so that we may develop strategies to manipulate musculoskeletal stem cells for treatments of congenital skeletal dysplasias, age-related skeletal diseases (osteoporosis and osteoarthritis), bone fractures, myelodysplasias, sarcopenia, neuromuscular degenerative disorders, and skeletal and hematopoietic related cancers
Program Faculty: Cheryl Ackert-Bicknell, Hani Awad, Danielle Benoit, Brendan Boyce, Laura Calvi, Joe Chakkalakal, Roman Eliseev, Jennifer Jonason, Catherine K. Kuo, Alayna Loiselle, J. Edward Puzas, Randy Rosier, Edward M. Schwarz, Lianping Xing, Xinping Zhang, Michael J. Zuscik