Chronic patellar tendinopathy is a degenerative tendon disorder characterized by chronic activity-related, anterior knee pain associated with localized tenderness, swelling and impaired performance, which is a common clinical problem in athletes. The pathogenesis of patellar tendinopathy is still largely unknown, although tendon overuse is the most commonly suggested etiological factor, and treatment is usually symptomatic. / Histopathologically, the predominant feature of patellar tendinopathy is tendinosis, which is characterized by progressive tissue degeneration with a failed healing response and the absence of inflammatory cells. Hypercellularity with non-tenocyte phenotype cells and tissue metaplasia, including hyaline metaplasia, fibrocartilaginous metaplasia and bony metaplasia were observed in clinical patellar tendinopathy samples. The degeneration of patellar tendon in patellar tendinopathy is an active cell-mediated process rather than a passive degenerative process. Using a patellar tendinopathy animal model, we observed the presence of chondrocytic and osteoblastic phenotype / markers in patellar tendinopathy samples with or without ossification, which was consistent with the findings in clinical samples. Interestingly, chondrocyte makers were expressed by healing tendon cells at week 2 which became round prior to their expression in the chondrocyte-like cells at week 4. This leads us to speculate that erroneous differentiation of tendon-derived stem cells (TDSCs) identified recently in tendon tissues by our group, to chondrocyte / osteoblasts, due to alteration of mechanical and biological microenvironment during overuse, may lead to the ectopic chondro-ossification and failed healing in patellar tendinopathy. Osteo-chondrogenic BMPs, such as BMP-2, BMP-4 and BMP-7 might be possible factors regulating the osteo-chondrogenic differentiation of TDSCs in the pathogenesis of patellar tendinopathy. / In conclusion, our results have provided new insights about the pathological mechanisms of patellar tendinopathy involving the resident stem cells, osteo-chondrogenic BMPs and mechanical overloading. Erroneous differentiation of TDSCs to chondrocytes / osteoblasts due to ectopic osteo-chondrogenic BMP-2 expression, which were induced by repetitive tensile loading stimulation, might account for the chondro-ossification and failed healing in patellar tendinopathy. Re-directing of stem cells for tenogenic differentiation by blocking the ectopic expression of osteo-chondrogenic BMPs may help to promote tendon healing in patellar tendinoapthy. / In this study, we hypothesized that (1) TDSCs isolated from pathological patellar tendon of the CI model will exhibit higher osteogenic and chondrogenic differentiation potential but lower proliferative capacity compared to TDSCs isolated from healthy patellar tendon. Rat pathological tendon in our collagenase-induced failed healing animal model will harbor more TDSCs compared to healthy patellar tendon. (2) Osteo-chondrogenic BMPs, such as BMP-2, BMP-4, and BMP-7, will be expressed ectopically in both preclinical and clinical samples of patellar tendinopathy. (3) BMP-2 will promote osteo-chondrogenic differentiation and inhibit tenogenic differentiation of TDSCs in vitro. (4) Repetitive tensile loading will increase the expression of BMP-2 in TDSCs in vitro. / Our results showed that TDSCs isolated from the collagenase-induced tendinopathic patellar tendon of the animal model exhibited higher osteogenic/chondrogenic differentiation potential as well as lower proliferative capacity, supporting that there might be some defects in the TDSCs from the animal model, which might undergo osteo-chondrogenic differentiation and hence reduced the pool of TDSCs for tendon repair in the development of patellar tendinopathy. The higher clonogenicity and increased yield of TDSCs in tendinopathic patellar tendon might be caused by a compensation for the impaired differentiation potential and proliferative capacity of TDSCs. The histopathological features of our clinical patellar tendinopathy were characterized by tissue degeneration. Non-tenocyte phenotype cells and tissue metaplasia, such as chondrocyte-like cells and endochondral ossification were also observed. We observed the ectopic expression of osteo-chondrogenic BMP-2, BMP-4 and BMP-7 in both our animal model and clinical samples of patellar tendinopathy, which might trigger the erroneous differentiation of TDSCs to non-tenocytes. Indeed, we further showed that BMP-2 could promote the osteo-chondrogenic and inhibit tenogenic differentiation of TDSCs in vitro, which might provide a possible explanation for ectopic chondro-ossification and failed healing in patellar tendinopathy. In addition, our results also showed that in vitro repetitive cyclic tensile loading could increase the expression of BMP-2 in TDSCs, which might provide a possible explanation for the ectopic expression of BMP-2 in patellar tendinopathy. / This study aimed to compare the osteogenic / chondrogenic differentiation potential, proliferative capacity and yield of TDSCs isolated from rat healthy patellar tendon and pathological tendon in our collagenase-induced failed tendon healing animal model of patellar tendinopathy in vitro. The histopathological characteristics of our clinical patellar tendinopathy with or without ossification were examined. The ectopic expression of BMP-2, BMP-4, and BMP-7 in both human and rat samples of patellar tendinopathy was also examined. The effects of BMP-2 on the osteogenic, chondrogenic and tenogenic differentiation of TDSCs was further investigated in vitro. The effect of repetitive tensile loading on the expression of BMP-2 in TDSCs was studied in vitro. / Rui, Yunfeng. / Advisers: Kai Ming Chan; Po Yee Lui. / Source: Dissertation Abstracts International, Volume: 73-06, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 172-193). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.
| Identifer | oai:union.ndltd.org:cuhk.edu.hk/oai:cuhk-dr:cuhk_344986 |
| Date | January 2011 |
| Contributors | Rui, Yunfeng., Chinese University of Hong Kong Graduate School. Division of Orthopaedics and Traumatology. |
| Source Sets | The Chinese University of Hong Kong |
| Language | English, Chinese |
| Detected Language | English |
| Type | Text, theses |
| Format | electronic resource, microform, microfiche, 1 online resource (xxii, 194, [56] leaves : col. ill.) |
| Rights | Use of this resource is governed by the terms and conditions of the Creative Commons “Attribution-NonCommercial-NoDerivatives 4.0 International” License (http://creativecommons.org/licenses/by-nc-nd/4.0/) |
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