Skip to main content
Download PDF
  • Research article
  • Open access
  • Published:

Parecoxib alleviates the inflammatory effect of leukocyte-rich platelet-rich plasma in normal rabbit tendons

BMC Musculoskeletal Disorders volume 21, Article number: 831 (2020) Cite this article

Abstract

Background

Platelet-rich plasma (PRP) is widely used to treat tendon injuries. Its therapeutic effect varies depending on the different cell components, and white blood cells (WBCs) may play an important role in this phenomenon. The purpose of this study was to evaluate how PRP with different concentrations of WBCs affect normal rabbit tendon and assess whether non-steroidal anti-inflammatory drugs (NSAIDs) can suppress the catabolic effects of WBCs.

Methods

Sixteen adult New Zealand White rabbits were used. Blood samples were collected from each rabbit, and PRP was extracted following two different protocols to obtain leukocyte-poor PRP (LP-PRP) and leukocyte-rich PRP (LR-PRP). LP-PRP or LR-PRP was injected into the patellar tendon of each rabbit, while normal saline (NS) was injected as control. In LR-PRP + NSAID group, Parecoxib was administered after LR-PRP injection. For each group, 2 rabbits were euthanatized at day 5 and 14. The patellar tendons were collected and stained with hematoxylin and eosin. A semi-quantitative approach was used to assess the inflammatory response and tendon destruction based on the evaluation of the WBCs, vascularization, fiber structure, and fibrosis.

Results

The LR-PRP group exhibited a higher total tendon score than the LP-PRP group at day 5 after PRP injection, but there was no significant difference between the two groups at day 14. For the NSAID group, the tendon score was lower than that of the LR-PRP group both at day 5 and 14.

Conclusion

LR-PRP can promote a higher inflammatory response than LP-PRP in the normal rabbit patellar tendon, and this effect can be suppressed by NSAIDs.

Peer Review reports

Background

Platelet-rich plasma (PRP) is characterized by a high concentration of platelets, and is prepared by centrifuging autologous whole blood samples collected with anticoagulants. After activation, PRP is rich in autologous growth factors, including the transforming growth factor (TGF-β1), platelet-derived growth factor (PDGF), and vascular endothelial growth factor (VEGF). These growth factors have the potential to stimulate the proliferation of fibroblasts (PDGF) [1], collagen synthesis (TGF-β) [2], differentiation of fibroblasts and myoblasts (IGF) [3], while VEGF and hepatocyte growth factor (HGF) have a synergic effect on angiogenesis [4]. For these reasons, the use of PRP for sports injury treatment has gradually increased [5,6,7]. Previous studies on PRP use are conflicting; some showed favorable results [8, 9], while others failed to reproduce these outcomes [10, 11]. Variations of the PRP extraction protocol used for different studies may play a role in the contradictory nature of these studies.

Some studies had shown negative outcomes after intramuscular PRP injection, including the infiltration of inflammatory cells, edema, and necrosis, during the early stage injection, followed by fibrosis in the chronic stage [12]. White blood cells (WBCs) produce various pro-inflammatory molecules, such as tumor necrosis factor–α (TNF-α) and interleukin-1β (IL-1β) [13], which are considered to be one of the causes of negative effects in sports injury treatments.

It has been reported that excessive inflammation is harmful for wound healing and tissue regeneration [14]. Parecoxib, a non-steroidal anti-inflammatory drug (NSAID), which is often used for postoperative pain management, selectively inhibits the activity of cyclooxygenase-2 (COX-2), and could be useful to control inflammation in the PRP-based treatment of tendon injuries [15, 16].

The aim of this study was to evaluate the inflammatory response caused by LR-PRP injection in normal rabbit tendon, coupled with Parecoxib administration. We hypothesized that LR-PRP will induce a higher inflammatory response and this effect can be suppressed by NSAID.

Methods

Animals

Sixteen adult New Zealand White rabbits (3–4 months old, 2.5–3.0 kg) were used in this study. The protocols for blood collection, tendon injection, and tendon collection from rabbits were approved by the Ethics Committee on the Care and Use of Animals of Chinese PLA General Hospital (Number 2016-X12–04), and all animals received humane care in strict accordance with the National Institutes of Health Guidelines.

Blood collection and PRP extraction

From each rabbit, 27 ml of whole blood was collected through the central artery of ear using an 18-gauge needle that was reloaded with 3.8% sodium citrate. Rabbits ware infused with 27 ml normal saline (NS) to recover the blood volume. For cell counting, 0.5 ml of the whole blood sample was used; the remaining blood was mixed with 3.8% sodium citrate in a 9:1 ratio, and then centrifuged at 200 g for 20 min. In the LR-PRP group, the plasma on the top layer and the buffy coat (containing mainly WBCs) from the middle layer were transferred to a new tube, and centrifuged at 400 g for another 15 min. In the LP-PRP group, only the plasma layer was transferred into a new centrifuge tube. After the second centrifugation step, the lower 4.5 ml was used as LR-PRP and LP-PRP. From this volume, 0.5 ml was used for cell counting, and the remaining 4 ml was used for injections (2 ml/knee).

Experimental procedures

Rabbits were anesthetized with ketamine (10 mg/kg) and xylazine (3 mg/kg). To ensure that all the tendon tissue was immersed with PRP or NS, 2 ml of solution was injected with a 25-gauge needle at 10 different points. (Fig. 1) Intra-tendon [17,18,19] and para-tendon [20] injection were both used in previous studies, but intra-tendon injection was adopted in our study to insure a full inflammation reaction. With the concern of tendon necrosis, a relatively low dose of media was injected and side effects such as necrosis was not observed in previous study [21].

Fig. 1
figure 1

Normal saline was injected into patellar tendon. Total 2 ml media was injected at 10 different points. LP-PRP and LR-PRP was injected with the same method

Full size image

A total of 16 healthy rabbits (32 patellar tendons) were used in this study. The animals were divided into 4 groups: control (NS-injected), LP-PRP, LR-PRP, and LR-PRP + NSAID. There were 4 animals (8 tendons) in each group. In control group, 2 ml NS was injected in each patellar tendon (4 animals, total 8 tendons). In LP-PRP group, 2 ml LP-PRP was injected in each patellar tendon (4 animals, total 8 tendons). In LR-PRP group and LR-PRP + NSAID group, 2 ml LR-PRP was injected in each patellar tendon (8 animals, total 16 tendons). Additionally, rabbits in LR-PRP + NSAID group were injected with Parecoxib (Pharmacia & Upjohn Company LLC, Kalamazoo, MI) 0.5 mg/kg intramuscularly every 24 h for 3 days. Rabbits were then caged individually and allowed to move freely.

Sample collection and histological analysis

Animals were euthanatized 5 or 14 days after PRP administration through lethal dose injection of ketamine (10 mg/kg) and xylazine (3 mg/kg). From each group, 2 animals (4 tendons) were euthanized at day 5, and the other 2 at day 14. The entire patellar tendon was removed from the patellar to the tibia insertion site, fixed in 10% buffered formalin for 48 h, and embedded in paraffin. The samples were cut into 5 μm-thick sections, and stained with hematoxylin-eosin (HE) for histological analysis. All sections were analyzed under a microscope by two doctors in a blinded manner.

Sections were systematically assessed using the 40× objective, and 4 fields were selected within the treatment areas, which were characterized by tendon fiber destruction following PRP injection.

A semi-quantitative grading scheme [21] was used to evaluate the intensity of the inflammatory response based on the WBC number, vascularization, fiber structure, and fibrosis on a scale from 0 to 3. In this scheme, a high score suggests a high tendon inflammatory response.

Statistical analysis

All results are represented as mean and standard deviation. Analysis of variance (ANOVA) was used for statistical analysis and the least significance difference (LSD) was used as post-hoc test. A difference of p < 0.05 was considered to be statistically significant.

Results

Analysis of autologous blood product

Compared to whole blood (WB), LP-PRP (2.06-fold) and LR-PRP (2.96-fold) had a higher platelet concentration; moreover, LR-PRP had a higher concentration of platelets and WBCs compared to LP-PRP. The results are shown in Table 1.

Table 1 Analysis of autologous blood products
Full size table

Histological findings

The LR-PRP group had a higher total tendon score than the LP-PRP group at day 5 post-injection (3.25, 95%CI 1.46 to 5.04, p = 0.002), but there was no significant difference between the two groups at day 14 (1.75, 95%CI − 0.21 to 3.71, p = 0.76). For the LR-PRP + NSAID group, the tendon score was lower than that of the LR-PRP group both at day 5 (2.25, 95%CI 0.46 to 4.04, p = 0.018) and day 14 (4.00, 95%CI 2.04 to 5.96, p = 0.001). The results are summarized in Table 2 and Table 3. The histological images are presented in Fig. 2 and Fig. 3.

Table 2 Histologic Data at day 5 post-injection
Full size table
Table 3 Histologic Data at day 14 post-injection
Full size table
Fig. 2
figure 2

Representative sections of rabbit patellar tendon stained with Haematoxylin and Eosin, 5 days post-injection. Tendons treated with NS (a) showing regular arrangement of parallel collagen fibrils and cell numbers. While treated with LP-PRP (b) and LR-PRP (c), tendon showing a higher inflammation reaction with a higher cell infiltration and fiber deterioration. LR-PRP has the highest inflammation reaction, but after NSAIDs was add (d), the reaction is alleviated. (HE, 400 × magnification)

Full size image
Fig. 3
figure 3

Representative sections of rabbit patellar tendon stained with Haematoxylin and Eosin, 14 days post-injection. Tendons treated with NS (a) showing relatively normal appearance. LP-PRP (b) and LR-PRP (c) has a comparable inflammation reaction and the cell infiltration is higher than 5 days. While in LR-PRP + NSAIDs group (d), the cell infiltration is lower than in LR-PRP group. (HE, 400 × magnification)

Full size image

Discussion

The most important finding of the study was that LR-PRP, which contained a higher concentration of WBCs compared to LP-PRP, induced a higher inflammation reaction in normal rabbit tendon and this effect could be alleviated by administration of NSAIDs both in acute (5 days) and chronic (14 days) phase. This result confirm our hypothesis that LR-PRP induces a higher inflammatory response and this effect can be suppressed by NSAID.

The tendon is a tissue with low blood supply and has a low healing rate after injury. PRP contains many growth factors that have the ability to promote tendon stem cell differentiation [22] and tenocyte proliferation [23], and it is believed to have the potential to accelerate tendon healing. This has been widely proven by many basic and clinical studies [9, 24,25,26]. While most of the studies showed favorable results, some also showed contrasting results. In the study conducted by Harris et al. [12], PRP has been shown to induce an increased inflammatory response in normal rabbit muscle tissues, which includes the infiltration of lymphocytes and monocytes, edema, necrosis, and fibrosis which might be harmful to tendon healing.

The reasons for this phenomenon remain unclear. One probable reason is that various cell components and cytokines play a role in tissue destruction. Leukocytes, which secrete vast amounts of TNF-α and IL-1β, are considered to be the most important source of pro-inflammatory cytokines [13]. In a rat tendon injury model, Marsolais et al. [27] showed that inflammatory cells, such as granulocytes, ED1, and ED2 macrophages, rapidly accumulate in the injury site. These types of cells contain high amounts of proteases that can damage the tendon tissue and delay injury healing [28]. Dragoo et al. [21] compared acute inflammatory response of two commercial PRP products with different WBCs concentration. The result showed that PRP with higher WBCs concentration caused a greater inflammatory response in acute phase in tendon tissue.

Our study confirmed that LR-PRP, which had a higher concentration of WBCs, induced a higher tendon score than LP-PRP at day 5, thereby showing that WBCs cause an intense inflammatory reaction in the acute phase. This result was consistent with the previous study [21]. In contrast, after 14 days, there was no significant difference between the LP-PRP and LR-PRP groups, showing that the inflammation caused by different PRP injections tends to be comparable in the chronic phase. Furthermore, we investigated whether the inflammation effect could be suppressed by NSAIDs, in which way the damage activity caused by inflammation could be suppressed.

In most PRP extraction methods, higher platelet concentrations often correspond to higher concentrations of WBCs. A recent study by Castillo et al. [29] compared the products from 3 different commercially available PRP separation systems. The authors emphasize that there was a significant difference between the WBC concentration in products obtained with different systems, as well as different platelet and growth factor concentrations. Therefore, repressing the tissue damage activity of WBCs might decrease the inflammatory response and enhance tissue regeneration.

NSAIDs are often used to alleviate the inflammation in injured tissues by inhibiting the activity of cyclooxygenase. This results in a decrease in the synthesis of prostaglandins, which are pro-inflammatory molecules that have the ability to recruit leukocytes and other immune cells at the injury site [30]. A previous study indicated that NSAIDs can also block the adhesion molecules on WBCs, decrease their migratory abilities, and thus, reduce tissue damage [31]. NSAIDs are reported to have 30–50% sparing effect on morphine consumption to release pain postoperatively [32]. As a highly selective COX-2 inhibitor, which has a lower side effect compare to non-selective COX inhibitor, parecoxib is frequently used to treat many orthopedics diseases [33,34,35]. We selected parecoxib in the study also because it is an injectable COX-2 inhibitor, [35] which is helpful for accurate drug administration in animal experiment.

Regarding their impact on platelet activation and aggregation, the combinatorial use of NSAIDs and PRP to treat tissue injuries was discouraged in the past. In a recent study, Anitua et al [36] examined if the intake of NSAIDs could affect the properties of platelets. The results showed that none of the tested NSAIDs affected platelet activation. In addition, the concentration of molecules that play important roles in tissue regeneration, such as VEGF, PDGF-AB, and IGF-1, was not altered.

Our study showed that the inflammatory reaction caused by WBCs can be suppressed by NSAIDs both in the acute and chronic phases, as the tendon scores were lower in the LR-PRP + NSAID group compared to the LR-PRP group, both after 5 and 14 days. Although administered only during the first 3 days, NSAIDs impact both the time points. This effect might not have only been caused by suppressing the synthesis of prostaglandins, but also by reducing the WBC recruitment ability that might account for the long-term effect.

The potential limitation of this study was that, we only observed the cellular and histological effects of WBC-induced inflammation, and further studies were required to elucidate the underlying molecular mechanisms. As mentioned above, Anitua et al [36] has proved that the intake of NSAIDs does not alter the biological properties of platelets in vitro, including the cytokine concentration of inflammation, cell proliferation, angiogenesis and cell migration. For this reason, we did not set a LP-PRP group to clarify the effect of NSAIDs on platelet. This could be another limitation of our study, in a following step, we need to test the histological effect of NSAIDs on platelet. For the reason that there is no ideal chronic tendinopathy model, only healthy tendons were analyzed in our study, a method which also adopted by previous study [21]; therefore, future studies should also include injured tendons to better simulate the clinical situation. Finally, the sample size was relatively low in our study, 95% CI was provided to better describe the result. Improvement in blood collection technique in smaller animals will help to increase the sample size in future study.

Conclusion

Our study confirms that LR-PRP can cause an increased inflammatory response in the normal rabbit patellar tendon that can be suppressed by NSAIDs. This shows that NSAIDs may be used to protect tendons from the pro-inflammatory activity of WBCs, which are present in PRP.

Availability of data and materials

The datasets used and analysed during the current study are available from the corresponding author on reasonable request.

Abbreviations

PRP:

Platelet-rich plasma

WBCs:

White blood cells

NSAIDs:

Non-steroidal anti-inflammatory drugs

LP-PRP:

Leukocyte-poor PRP

LR-PRP:

Leukocyte-rich PRP

NS:

Normal saline

TGF-β:

Transforming growth factor

PDGF:

Platelet-derived growth factor

VEGF:

Vascular endothelial growth factor

HGF:

Hepatocyte growth factor

References

  1. Heldin C-H, Westermark B. Mechanism of action and in vivo role of platelet-derived growth factor. Physiol Rev. 1999;79(4):1283–316.

    Article  CAS  Google Scholar 

  2. Shi Y, Massagué J. Mechanisms of TGF-β signaling from cell membrane to the nucleus. Cell. 2003;113(6):685–700.

    Article  CAS  Google Scholar 

  3. Danielpour D, Song K. Cross-talk between IGF-I and TGF-β signaling pathways. Cytokine Growth Factor Rev. 2006;17(1):59–74.

    Article  CAS  Google Scholar 

  4. Gerritsen ME, Tomlinson JE, Zlot C, Ziman M, Hwang S. Using gene expression profiling to identify the molecular basis of the synergistic actions of hepatocyte growth factor and vascular endothelial growth factor in human endothelial cells. Br J Pharmacol. 2003;140(4):595–610.

    Article  CAS  Google Scholar 

  5. Sanchez M, Anitua E, Orive G, Mujika I, Andia I. Platelet-rich therapies in the treatment of orthopaedic sport injuries. Sports Med. 2009;39(5):345–54.

    Article  Google Scholar 

  6. Lopez-Vidriero E, Goulding KA, Simon DA, Sanchez M, Johnson DH. The use of platelet-rich plasma in arthroscopy and sports medicine: optimizing the healing environment. Arthroscopy. 2010;26(2):269–78.

    Article  Google Scholar 

  7. Hall MP, Band PA, Meislin RJ, Jazrawi LM, Cardone DA. Platelet-rich plasma: current concepts and application in sports medicine. J Am Acad Orthop Surg. 2009;17(10):602–8.

    Article  Google Scholar 

  8. Sanchez M, Anitua E, Azofra J, Andia I, Padilla S, Mujika I. Comparison of surgically repaired Achilles tendon tears using platelet-rich fibrin matrices. Am J Sports Med. 2007;35(2):245–51.

    Article  Google Scholar 

  9. Kon E, Filardo G, Delcogliano M, Presti ML, Russo A, Bondi A, et al. Platelet-rich plasma: new clinical application: a pilot study for treatment of jumper's knee. Injury. 2009;40(6):598–603.

    Article  Google Scholar 

  10. de Vos RJ, Weir A, van Schie HTM, Bierma-Zeinstra SMA, Verhaar JAN, Weinans H, et al. Platelet-rich plasma injection for chronic Achilles tendinopathy. JAMA. 2010;303(2):144–9.

    Article  Google Scholar 

  11. Banfi G, Corsi MM, Volpi P. Could platelet rich plasma have effects on systemic circulating growth factors and cytokine release in orthopaedic applications? Br J Sports Med. 2006;40(10):816.

    Article  CAS  Google Scholar 

  12. Harris NL, Huffer WE, von Stade E, Larson AI, Phinney S, Purnell ML. The effect of platelet-rich plasma on normal soft tissues in the rabbit. J Bone Joint Surg Am. 2012;94(9):786–93.

    Article  Google Scholar 

  13. Sundman EA, Cole BJ, Fortier LA. Growth factor and catabolic cytokine concentrations are influenced by the cellular composition of platelet-rich plasma. Am J Sports Med. 2011;39(10):2135–40.

    Article  Google Scholar 

  14. El-Sharkawy H, Kantarci A, Deady J, Hasturk H, Liu H, Alshahat M, et al. Platelet-rich plasma: growth factors and pro-and anti-inflammatory properties. J Periodontol. 2007;78(4):661–9.

    Article  CAS  Google Scholar 

  15. Tsailas PG, Babis GC, Nikolopoulos K, Soucacos PN, Korres DS. The effectiveness of two COX-2 inhibitors in the prophylaxis against heterotopic new bone formation: an experimental study in rabbits. J Surg Res. 2009;151(1):108–14.

    Article  CAS  Google Scholar 

  16. Chong SJ, Wong YC, Wu J, Tan MH, Lu J, Moochhala SM. Parecoxib reduces systemic inflammation and acute lung injury in burned animals with delayed fluid resuscitation. Int J Inflamm. 2014;2014:92645.

  17. Albano D, Messina C, Usuelli FG, De Girolamo L, Grassi M, Maccario C, et al. Magnetic resonance and ultrasound in achilles tendinopathy: predictive role and response assessment to platelet-rich plasma and adipose-derived stromal vascular fraction injection. Eur J Radiol. 2017;95:130–5.

    Article  Google Scholar 

  18. Gonzalez JC, Lopez C, Alvarez ME, Perez JE, Carmona JU. Autologous leukocyte-reduced platelet-rich plasma therapy for Achilles tendinopathy induced by collagenase in a rabbit model. Sci Rep. 2016;6:19623.

    Article  CAS  Google Scholar 

  19. Krogh TP, Ellingsen T, Christensen R, Jensen P, Fredberg U, et al. Am J Sports Med. 2016;44(8):1990–7.

    Article  Google Scholar 

  20. Boesen AP, Hansen R, Boesen MI, Malliaras P, Langberg H. Effect of high-volume injection, platelet-rich plasma, and sham treatment in chronic Midportion Achilles Tendinopathy: a randomized double-blinded prospective study. Am J Sports Med. 2017;45(9):2034–43.

    Article  Google Scholar 

  21. Dragoo JL, Braun HJ, Durham JL, Ridley BA, Odegaard JI, Luong R, et al. Comparison of the acute inflammatory response of two commercial platelet-rich plasma Systems in Healthy Rabbit Tendons. Am J Sports Med. 2012;40(6):1274–81.

    Article  Google Scholar 

  22. Zhang J, Wang JH. Platelet-rich plasma releasate promotes differentiation of tendon stem cells into active tenocytes. Am J Sports Med. 2010;38(12):2477–86.

    Article  Google Scholar 

  23. Visser LC, Arnoczky SP, Caballero O, Kern A, Ratcliffe A, Gardner KL. Growth factor-rich plasma increases tendon cell proliferation and matrix synthesis on a synthetic scaffold: an in vitro study. Tissue Eng A. 2010;16(3):1021–9.

    Article  CAS  Google Scholar 

  24. Gaweda K, Tarczynska M, Krzyzanowski W. Treatment of Achilles tendinopathy with platelet-rich plasma. Int J Sports Med. 2010;31(08):577–83.

    Article  CAS  Google Scholar 

  25. Castricini R, Longo UG, De Benedetto M, Panfoli N, Pirani P, Zini R, et al. Platelet-rich plasma augmentation for arthroscopic rotator cuff repair: a randomized controlled trial. Am J Sports Med. 2011;39(2):258–65.

    Article  Google Scholar 

  26. Yamada N, Hamada K, Nakajima T, Kobayashi K, Fukuda H. Comparison of conservative and operative treatments of massive rotator cuff tears. Tokai J Exp Clin Med. 2000;25(4/6):151–64.

    CAS  PubMed  Google Scholar 

  27. Marsolais D, Cote CH, Frenette J. Neutrophils and macrophages accumulate sequentially following Achilles tendon injury. J Orthop Res. 2001;19(6):1203–9.

    Article  CAS  Google Scholar 

  28. Palmgren MS, de Shazo RD, Carter RM, Zimny ML, Shah SV. Mechanisms of neutrophil damage to human alveolar extracellular matrix: the role of serine and metalloproteases. J Allergy Clin Immunol. 1992;89(4):905–15.

    Article  CAS  Google Scholar 

  29. Castillo TN, Pouliot MA, Kim HJ, Dragoo JL. Comparison of growth factor and platelet concentration from commercial platelet-rich plasma separation systems. Am J Sports Med. 2011;39(2):266–71.

    Article  Google Scholar 

  30. Almekinders L. Anti-inflammatory treatment of muscular injuries in sport. Sports Med. 1999;28(6):383–8.

    Article  CAS  Google Scholar 

  31. Diaz-Gonzalez F, Gonzalez-Alvaro I, Campanero MR, Mollinedo F, del Pozo MA, Munoz C, et al. Prevention of in vitro neutrophil-endothelial attachment through shedding of L-selectin by nonsteroidal antiinflammatory drugs. J Clin Invest. 1995;95(4):1756–65.

    Article  CAS  Google Scholar 

  32. Marret E, Kurdi O, Zufferey P, Bonnet F, Warltier DC. Effects of nonsteroidal Antiinflammatory drugs on patient-controlled analgesia morphine side effects: meta-analysis of randomized controlled trials. Anesthesiology. 2005;102(6):1249–60.

    Article  CAS  Google Scholar 

  33. Riest G, Peters J, Weiss M, Dreyer S, Klassen PD, Stegen B, et al. Preventive effects of perioperative parecoxib on post-discectomy pain. Br J Anaesth. 2008;100(2):256–62.

    Article  CAS  Google Scholar 

  34. Laine L, White WB, Rostom A, Hochberg M. COX-2 selective inhibitors in the treatment of osteoarthritis. Semin Arthritis Rheum. 2008;38(3):165–87.

    Article  CAS  Google Scholar 

  35. Jean YH, Wen ZH, Chang YC, Hsieh SP, Tang CC, Wang YH, et al. Intra-articular injection of the cyclooxygenase-2 inhibitor parecoxib attenuates osteoarthritis progression in anterior cruciate ligament-transected knee in rats: role of excitatory amino acids. Osteoarthr Cartil. 2007;15(6):638–45.

    Article  Google Scholar 

  36. Anitua E, Troya M, Zalduendo MM, Orive G. The effect of different drugs on the preparation and biological outcomes of plasma rich in growth factors. Annals of anatomy =. Anat Anz. 2014;196(6):423–9.

    Article  Google Scholar 

Download references

Acknowledgements

Not applicable.

Funding

This study was supported by National Natural Science Foundation (81401808). The funding body has not been involved in the design, data collection, analysis, interpretation or the writing of the manuscript.

Author information

Authors and Affiliations

  1. Department of Rehabilitation Medicine, First Medical Center of Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, People’s Republic of China

    Ming Zhou, Ning Wang, Gang Wang, Zishan Jia & Xiaolei Qi

Authors
  1. Ming Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ning Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gang Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zishan Jia
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xiaolei Qi
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Experimental Design: NW, ZSJ; Conducting Experiments: MZ, NW, XLQ, GW; Collecting Data: MZ, NW; Statistical Analysis: MZ, NW; Data Interpretation: MZ, NW, GW, ZSJ; Manuscript Preparation: MZ, NW. The author(s) read and approved the final manuscript.

Corresponding author

Correspondence to Ning Wang.

Ethics declarations

Ethics approval and consent to participate

The protocols for blood collection, tendon injection, and tendon collection from rabbits were approved by the Ethics Committee on the Care and Use of Animals of Chinese PLA General Hospital (Number 2016-X12–04), and all animals received humane care in strict accordance with the National Institutes of Health Guidelines.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhou, M., Wang, N., Wang, G. et al. Parecoxib alleviates the inflammatory effect of leukocyte-rich platelet-rich plasma in normal rabbit tendons. BMC Musculoskelet Disord 21, 831 (2020). https://doi.org/10.1186/s12891-020-03793-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s12891-020-03793-2

Keywords

BMC Musculoskeletal Disorders

ISSN: 1471-2474

Contact us