Ling Qin

faculty photo
Associate Professor of Orthopaedic Surgery
Member, Penn Center for Musculoskeletal Disorders
Member, Penn Center for Musculoskeletal Disorders
Member, Abramson Cancer Center of the University of Pennsylvania
Co-Director of Histology Core, Penn Center for Musculoskeletal Disorders
Department: Orthopaedic Surgery

Contact information
McKay Orthopaedic Research Laboratory
G14A Stemmler Hall
3450 Hamilton Walk
Philadelphia, PA 19104
Office: 215-898-6697
Fax: 215-573-2133
Lab: 215-898-3261
Graduate Group Affiliations
BS (Bioscience and Technology)
Shanghai Jiao Tong University, 1992.
Ph.D. (Biochemistry)
UMDNJ-Robert Wood Johnson Medical School, 2001.
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Description of Itmat Expertise

The adult human skeleton continuously undergoes remodeling, namely, being resorbed by osteoclasts and renewed by osteoblasts. The maintenance of the skeleton requires the coordinated activities and constant generation of these cells. Disruption of this coordination underlies many bone diseases, such as osteoporosis and cancer-associated bone loss. These diseases cause great morbidity and mortality in the elderly and bone metastasized cancer patients and therefore are major public health problems worldwide. A variety of growth factors and hormones play important roles in bone metabolism. Our laboratory focuses on epidermal growth factor receptor (EGFR) and its ligands and uses a combination of molecular, biochemical, imaging and animal techniques to understand the molecular mechanisms of how this signaling pathway network regulates bone metabolism and skeletal development.

Description of Research Expertise

Area of Expertise:

Bone metabolism, stem cell biology, growth plate development, cancer bone metastasis, and signal transduction

Area of Special Interest:

The human skeleton is a dynamic tissue, constantly undergoing remodeling through coupled activities of two cells: the bone-resorbing osteoclast and the bone-forming osteoblast. A shift in the balance of these two actions toward resorption leads to osteoporosis, a silent disease characterized by excessive bone loss and micro-architectural deterioration of bone tissue leading to bone fragility and fracture. Osteoblasts are derived from mesenchymal progenitors, including mesenchymal stem cells (MSCs) and committed osteoprogenitors. Convincing evidence suggests that there are decreases in the number and proliferative capacity and increases in senescence and apoptosis of mesenchymal progenitors in aging and osteoporotic populations. Bone formation by osteoblast lineage cells is controlled by a variety of growth factors and hormones. Our laboratory is interested in understanding their downstream signaling pathways that regulate the biology of bone formation, with a special focus on parathyroid hormone (PTH1-34, teriparatide), the only FDA-approved anabolic treatment for osteoporosis.

One area of our interest is addressing the essential role of epidermal growth factor receptor (EGFR) in regulating bone marrow mesenchymal progenitor pool and mediating the effect of PTH on bone formation. We have demonstrated that amphiregulin, an EGFR ligand, is one of the highest PTH-stimulated genes in osteoblasts and osteocytes. Activation of EGFR signaling in mesenchymal progenitors stimulates their proliferation, survival, and migration. Blocking EGFR activity in mice leads to defective bone formation and an osteopenic phenotype which are accompanied by a reduction in the number of mesenchymal progenitors. More importantly, mice deficient in osteoblast lineage EGFR activity have a poor anabolic response to PTH-induced bone formation. We utilize transgenic and pharmacological mouse models in combination with molecular, biochemical, and imaging assays for these studies.

Our second line of interest is investigating molecular mechanisms by which PTH treatment rescues bone loss and osteoporosis induced by radiotherapy. Radiotherapy is often used to eliminate tumor cells but it has negative effects on neighboring normal tissues including bone, causing acute and chronic problems such as osteoradionecrosis, osteoporosis, and fractures. The primary radiation damage to bone is local tissue atrophy, characterized by loss of functional osteoblasts, marrow adiposity, and microvascular impairment. We found that daily injections of PTH1-34 largely prevents bone loss and deterioration of bone structure in irradiated rodent bone and that the major mechanism appears to be protection of mature osteoblasts and bone marrow mesenchymal progenitors. One interesting finding is that PTH is capable of promoting DNA double strand break (DSB) repair in irradiated osteoblasts and thus protecting osteoblasts from radiation-induced cell death. Innovative approaches, such as small animal radiation research platform (SARRP) that replicates the effects of focal radiation therapy, in vivo µCT imaging and longitudinal tracking of the same trabecular bone, and lineage tracing in genetically modified mouse models are used for this project.

The third area of interest is identifying and functionally characterizing a distinct mesenchymal progenitor population within bone marrow. Mesenchymal progenitor cells are traditionally isolated from the central region of long bones (central mesenchymal progenitors) and therefore, they are distant from bone surface. We have established a unique enzymatic digestion approach to isolate endosteal bone marrow cells that are close to bone surface and found that they contain a much higher frequency of mesenchymal progenitors than central bone marrow cells. We further demonstrated that endosteal mesenchymal progenitors have superior proliferation, greater immunosuppressive activity, and more responsiveness toward aging and PTH injection than central mesenchymal progenitors and therefore, represent a biologically important target for future mesenchymal stem cell studies. We are currently exploring the difference between these two populations of bone marrow mesenchymal progenitors with a special interest on their interactions with surrounding bone marrow environment.

Lastly, our group is interested in delineating the critical role of EGFR in regulating cartilage extraceullar matrix degradation. Growth plate development is a critical step in endochondral bone formation and longitudinal bone growth. This process, including chondrocyte proliferation, maturation, mineralization, matrix remodeling and transition from cartilage to bone, is tightly controlled by circulating systemic hormones and locally produced growth factors. We recently found that rodents lacking of chondrogenic EGFR activity develop profound defects in growth plate cartilage characterized by epiphyseal growth plate thickening and massive accumulation of hypertrophic chondrocytes. The underlying mechanisms include stimulating the chondrogenic expression of matrix metalloproteinases (MMPs) and promoting osteoclastogenesis at the chondro-osseous junction. Study of this project will shed new light on growth defect diseases, such as chondrodysplasia, retarded growth and reduced final height, and degenerative cartilage diseases, such as osteoarthritis.

Selected Publications

Chandra, A., Lin, T., Young, T., Tong, W., Ma, X., Tseng, W.J., Kramer, I., Kneissel, M., Levine, M.A., Zhang, Y., Cengel, K., Liu, X.S., and Qin, L. : Suppression of Sclerostin alleviates radiation-induced bone loss by protecting bone forming cells and their progenitors through distinct mechanisms. J. Bone Miner. Res. 32: 360-372, 2017.

Doyran, B.#, Tong, W.#, Li, Q., Jia, H., Zhang, X., Chen, C., Enomoto-Iwamoto, M., Lu, X.L., Qin, L.*, and Han, L*. #: these authors contributed equally to this work. *: both authors are corresponding authors.: Nanoindentation modulus of murine cartilage: a sensitive indicator of the initiation and progression of post-traumatic osteoarthritis. Osteoarthritis Cartilage 25: 108-117, 2017.

Zhu, H., Xie, F., Luo, X., Qin, L., Liu, X.S., Levine, L.S., and Li, Q. : Orthotopic forelimb allotransplantation in the rat model. Microsurgery 36(8): 672-675. Nov. 2016.

Shi, P., Chen E.Y., Cs-Szabo, G., Chee, A., Tanoury, C., Qin, L., Lin, H., An, S., An, H.S., and Zhang, Y. : Biglycan Inhibits Capsaicin-Induced Substance P Release by Cultured Dorsal Root Ganglion Neurons. Am. J. Phys. Med. Rehabil. 95(9): 656-662. Sept. 2016.

Wang, Y., Dellatore, P., Douard, V., Qin, L., Watford, M., Ferraris, R.P., Lin, T., and Shapses, S.A. : High fat diet enriched with saturated, but not monounsaturated fatty acids adversely affects femur, and both diets increase calcium absorption in older female mice. Nutr Res. 36(7): 742-750. July 2016.

Candela, M.E., Wang, C., Gunawardena, A.T., Zhang, K., Cantley, L., Yasuhara, R., Usami, Y., Francois, N., Iwamoto, M., van der Flier, A., Zhang, Y., Qin, L., Han, L., and Enomoto-Iwamoto, M. : Alpha 5 Integrin mediates osteoarthritic changes in mouse knee joints. PLoS One. 11(6): e0156783, June 2016.

Jia, H.*, Ma, X.*, Tong, W.*, Doyan, B., Sun, Z., Wang, L., Zhang, X., Zhou, Y., Badar, F., Chandra, A., Lu, X.L., Xia, Y., Han, L., Enomoto-Iwamoto, M., and Qin, L. * these authors contributed equally to this paper. : EGFR signaling is critical for maintaining the superficial layer of articular cartilage and preventing osteoarthritis initiation. Proc. Natl. Acad. Sci. USA Page: in press, 2016.

Li, Q., Doyran, B., Gamer, L.W., Lu, X.L., Qin, L., Ortiz, C., Grodzinsky, A.J., Rosen, V. & Han, L.: Biomechanical properties of murine meniscus surfaces via AFM-based nanoindentation. Journal of Biomechanics 48: 1364-1370, June 2015.

de Bakker, C.M.J., Altman, A.R., Tseng, W., Tribble, M.B., Li, C., Chandra, A., Qin, L., and Liu, X.S.: µCT-Based, in vivo dynamic bone histomorphometry allows 3D evaluation of the early responses of bone resorption and formation to PTH and Alendronate combination therapy. Bone 73: 198-207, April 2015.

Scanzello, C.R., Markova, D.Z., Chee, A., Xiu, Y., Adams, S.L., Anderson, G., Zgonis, M., Qin, L., An, H.S., and Zhang, Y.: Fibronectin splice variation in human knee cartilage, meniscus and synovial membrane: observations in osteoarthritic knee. J. Orthop. Res. 33: 556-562, April 2015.

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Last updated: 07/18/2018
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