Suppression of osteogenic activity by regulation of WNT and BMP signaling during titanium particle induced osteolysis
Ju-Suk Nam
Institute for Skeletal Aging & Orthopedic Surgery, Hallym University-Chuncheon Sacred Heart Hospital, Chuncheon, 24252 Republic of Korea
These authors contributed equally to this work.
Search for more papers by this authorAshish Ranjan Sharma
Institute for Skeletal Aging & Orthopedic Surgery, Hallym University-Chuncheon Sacred Heart Hospital, Chuncheon, 24252 Republic of Korea
These authors contributed equally to this work.
Search for more papers by this authorSupriya Jagga
Institute for Skeletal Aging & Orthopedic Surgery, Hallym University-Chuncheon Sacred Heart Hospital, Chuncheon, 24252 Republic of Korea
Search for more papers by this authorDong-Hyun Lee
Institute for Skeletal Aging & Orthopedic Surgery, Hallym University-Chuncheon Sacred Heart Hospital, Chuncheon, 24252 Republic of Korea
Search for more papers by this authorGarima Sharma
Institute for Skeletal Aging & Orthopedic Surgery, Hallym University-Chuncheon Sacred Heart Hospital, Chuncheon, 24252 Republic of Korea
Search for more papers by this authorLich Thi Nguyen
Institute for Skeletal Aging & Orthopedic Surgery, Hallym University-Chuncheon Sacred Heart Hospital, Chuncheon, 24252 Republic of Korea
Search for more papers by this authorYeon Hee Lee
Institute for Skeletal Aging & Orthopedic Surgery, Hallym University-Chuncheon Sacred Heart Hospital, Chuncheon, 24252 Republic of Korea
Search for more papers by this authorJun-Dong Chang
Institute for Skeletal Aging & Orthopedic Surgery, Hallym University-Chuncheon Sacred Heart Hospital, Chuncheon, 24252 Republic of Korea
Search for more papers by this authorChiranjib Chakraborty
Institute for Skeletal Aging & Orthopedic Surgery, Hallym University-Chuncheon Sacred Heart Hospital, Chuncheon, 24252 Republic of Korea
Department of Bio-informatics, School of Computer and Information Sciences, Galgotias University, Greater Noida, 203201 India
Search for more papers by this authorCorresponding Author
Sang-Soo Lee
Institute for Skeletal Aging & Orthopedic Surgery, Hallym University-Chuncheon Sacred Heart Hospital, Chuncheon, 24252 Republic of Korea
Correspondence to: S.-S. Lee, MD, PhD; e-mail: [email protected] or [email protected]Search for more papers by this authorJu-Suk Nam
Institute for Skeletal Aging & Orthopedic Surgery, Hallym University-Chuncheon Sacred Heart Hospital, Chuncheon, 24252 Republic of Korea
These authors contributed equally to this work.
Search for more papers by this authorAshish Ranjan Sharma
Institute for Skeletal Aging & Orthopedic Surgery, Hallym University-Chuncheon Sacred Heart Hospital, Chuncheon, 24252 Republic of Korea
These authors contributed equally to this work.
Search for more papers by this authorSupriya Jagga
Institute for Skeletal Aging & Orthopedic Surgery, Hallym University-Chuncheon Sacred Heart Hospital, Chuncheon, 24252 Republic of Korea
Search for more papers by this authorDong-Hyun Lee
Institute for Skeletal Aging & Orthopedic Surgery, Hallym University-Chuncheon Sacred Heart Hospital, Chuncheon, 24252 Republic of Korea
Search for more papers by this authorGarima Sharma
Institute for Skeletal Aging & Orthopedic Surgery, Hallym University-Chuncheon Sacred Heart Hospital, Chuncheon, 24252 Republic of Korea
Search for more papers by this authorLich Thi Nguyen
Institute for Skeletal Aging & Orthopedic Surgery, Hallym University-Chuncheon Sacred Heart Hospital, Chuncheon, 24252 Republic of Korea
Search for more papers by this authorYeon Hee Lee
Institute for Skeletal Aging & Orthopedic Surgery, Hallym University-Chuncheon Sacred Heart Hospital, Chuncheon, 24252 Republic of Korea
Search for more papers by this authorJun-Dong Chang
Institute for Skeletal Aging & Orthopedic Surgery, Hallym University-Chuncheon Sacred Heart Hospital, Chuncheon, 24252 Republic of Korea
Search for more papers by this authorChiranjib Chakraborty
Institute for Skeletal Aging & Orthopedic Surgery, Hallym University-Chuncheon Sacred Heart Hospital, Chuncheon, 24252 Republic of Korea
Department of Bio-informatics, School of Computer and Information Sciences, Galgotias University, Greater Noida, 203201 India
Search for more papers by this authorCorresponding Author
Sang-Soo Lee
Institute for Skeletal Aging & Orthopedic Surgery, Hallym University-Chuncheon Sacred Heart Hospital, Chuncheon, 24252 Republic of Korea
Correspondence to: S.-S. Lee, MD, PhD; e-mail: [email protected] or [email protected]Search for more papers by this authorAbstract
Periprosthetic osteolysis remains the leading obstacle for total joint replacements. Primarily, it was thought that aseptic loosening is mainly caused by macrophage mediated inflammatory process arising from production of wear debris. The role of osteoclasts and its sequential bone resorption ability has been extensively studied, but little is known about impaired osteogenesis during osteolysis. In the current study, we have tried to delineate the regulatory mechanism of osteogenic signals by Ti particles in osteoprogenitor cells as well its participatory role in wear debris induced osteolysis. Implantation of Ti particles on mice calvaria induced pro-inflammatory response, elevated expression of COX2 and reduced the expression of Osterix. Treatment of Ti particles to MC3T3 E-1 cells displayed decreased osteogenic activity including ALP activity, mineralization and mRNA levels several osteogenic genes. Moreover, the basal activity of WNT and BMP signaling pathways was suppressed in MC3T3 E-1 cells treated with Ti particles. As an early response to Ti particles, MC3T3 E-1 cells showed activation of ERK and JNK. Co-inhibition of ERK and JNK with their specific inhibitors resulted in partial recovery of WNT and BMP signaling activity as well as ALP activity and collagen synthesis. Finally, LiCl mediated activation of WNT signaling pathway demonstrated rescue of Ti particle facilitated suppression of Osterix expression in mice calvaria. Our results provide evidences that WNT signaling pathway is regulated by ERK, JNK, and BMP signaling pathway during wear debris induced inflammatory osteolysis and may be considered as suitable therapeutic targets for the treatment. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 912–926, 2017.
Supporting Information
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