Intra-articular Injection of Pure Platelet-Rich Plasma Is the Most Effective Treatment for Joint Pain by Modulating Synovial Inflammation and Calcitonin Gene-Related Peptide Expression in a Rat Arthritis Model

Araya, Naoko; Miyatake, Kazumasa; Tsuji, Kunikazu; Katagiri, Hiroki; Nakagawa, Yusuke; Hoshino, Takashi; Onuma, Hiroaki; An, Saisei; Nishio, Hirofumi; Saita, Yoshitomo; Sekiya, Ichiro; Koga, Hideyuki

doi:10.1177/0363546520924011

Cited by 29 publications

(26 citation statements)

References 42 publications

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“…Another problem often associated with PRP that is the content of leukocytes in PRP. In a rat arthritis model, Araya et al [ 50 ] showed that intra-articular injection of pure PRP was the most effective treatment for inhibition of the progression of synovitis and reduction of pain. They compared pure PRP, leukocyte-pure PRP and leukocyte-rich PRP to clarify the optimal PRP formulation.…”

Section: Animal Studiesmentioning

confidence: 99%

The Effect of Platelet-Rich Plasma on the Intra-Articular Microenvironment in Knee Osteoarthritis

Szwedowski

Szczepanek

Paczesny³

et al. 2021

IJMS

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Knee osteoarthritis (KOA) represents a clinical challenge due to poor potential for spontaneous healing of cartilage lesions. Several treatment options are available for KOA, including oral nonsteroidal anti-inflammatory drugs, physical therapy, braces, activity modification, and finally operative treatment. Intra-articular (IA) injections are usually used when the non-operative treatment is not effective, and when the surgery is not yet indicated. More and more studies suggesting that IA injections are as or even more efficient and safe than NSAIDs. Recently, research to improve intra-articular homeostasis has focused on biologic adjuncts, such as platelet-rich plasma (PRP). The catabolic and inflammatory intra-articular processes that exists in knee osteoarthritis (KOA) may be influenced by the administration of PRP and its derivatives. PRP can induce a regenerative response and lead to the improvement of metabolic functions of damaged structures. However, the positive effect on chondrogenesis and proliferation of mesenchymal stem cells (MSC) is still highly controversial. Recommendations from in vitro and animal research often lead to different clinical outcomes because it is difficult to translate non-clinical study outcomes and methodology recommendations to human clinical treatment protocols. In recent years, significant progress has been made in understanding the mechanism of PRP action. In this review, we will discuss mechanisms related to inflammation and chondrogenesis in cartilage repair and regenerative processes after PRP administration in in vitro and animal studies. Furthermore, we review clinical trials of PRP efficiency in changing the OA biomarkers in knee joint.

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Section: Animal Studiesmentioning

confidence: 99%

The Effect of Platelet-Rich Plasma on the Intra-Articular Microenvironment in Knee Osteoarthritis

Szwedowski

Szczepanek

Paczesny³

et al. 2021

IJMS

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“…Very similar data were obtained in another study, where processed lipo-aspirate was injected into the rat joint after OA induction via MIA, leading to pain relief and anti-inflammatory responses [ 152 ]. Using the same OA model, another group observed a strong reduction of αCGRP-positive nerve fibers in the infrapatellar fat pad after treatment with platelet rich plasma (PRP) and associated this with the reduction of joint pain analysis of weight-bearing distribution with an incapacitance tester [ 153 ]. An increase in CGRP positive nerve fiber density was also observed in synovial tissue after MIA induced knee OA [ 154 ].…”

Section: Impact Of the Peripheral Nervous System And Its Neuropeptides On Oamentioning

confidence: 99%

Osteoarthritis: Novel Molecular Mechanisms Increase Our Understanding of the Disease Pathology

Grässel

Zaucke

Madry

2021

JCM

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Although osteoarthritis (OA) is the most common musculoskeletal condition that causes significant health and social problems worldwide, its exact etiology is still unclear. With an aging and increasingly obese population, OA is becoming even more prevalent than in previous decades. Up to 35% of the world’s population over 60 years of age suffers from symptomatic (painful, disabling) OA. The disease poses a tremendous economic burden on the health-care system and society for diagnosis, treatment, sick leave, rehabilitation, and early retirement. Most patients also experience sleep disturbances, reduced capability for exercising, lifting, and walking and are less capable of working, and maintaining an independent lifestyle. For patients, the major problem is disability, resulting from joint tissue destruction and pain. So far, there is no therapy available that effectively arrests structural deterioration of cartilage and bone or is able to successfully reverse any of the existing structural defects. Here, we elucidate novel concepts and hypotheses regarding disease progression and pathology, which are relevant for understanding underlying the molecular mechanisms as a prerequisite for future therapeutic approaches. Emphasis is placed on topographical modeling of the disease, the role of proteases and cytokines in OA, and the impact of the peripheral nervous system and its neuropeptides.

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“…64 Calcitonin gene-related peptide expression mediates pain reduction and down-regulation of synovial inflammation induced by PRP. 65 Advanced biomarkers, both anatomic and soluble biomarkers, reflecting several pathophysiological mechanisms, have been researched extensively, 66,67 mainly in the Osteoarthritis Research Society International (OARSI) framework, to improve OA management. 68 Accordingly, OA phenotypes were defined as 'subtypes of OA that share distinct underlying pathobiological and pain mechanisms and different course of the disease', merging in similar structural changes in final stages.…”

Section: How Work Performed In Oa Phenotyping Might Impact Prp Therapmentioning

confidence: 99%

Moving toward targeting the right phenotype with the right platelet-rich plasma (PRP) formulation for knee osteoarthritis

Andı́a

Atilano

Maffulli

2021

Therapeutic Advances in Musculoskeletal

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Intra-articular injections of platelet-rich plasma (PRP) and other novel blood-derived products developed specifically for osteoarthritis (OA) can provide pain relief and potential benefits in disease progression. Meta-analyses show the clinical superiority of PRP compared with other intra-articular injections, but results are modest and the effect sizes are small. PRP injections in knee OA are performed indiscriminately, but the clinical response varies enormously between patients because of an array of mixed OA phenotypes. Subgroup analyses are scarce; some studies stratify patients according to radiographic severity and found better results in early OA, without consensus for more advanced stages of the condition. Parallel identification of soluble and imaging biomarkers is essential to personalise and leverage PRP therapies. The inflammatory phenotype is most interesting from the PRP perspective because PRPs modulate inflammation by releasing a large pool of chemokines and cytokines, which interact with synovial fibroblasts and macrophages; in addition, they can modulate the innate immune response. No soluble biomarkers have been discovered that have implications for OA research and PRP interventions. Clinical examination of patients based on their inflammatory phenotype and imaging identification of pain sources and structural alterations could help discern who will respond to PRP. Synovial inflammation and bone marrow lesions are sources of pain, and intra-articular injections of PRP combined with subchondral bone injection can enhance clinical outcomes. Further refining ultrasound phenotypes may aid in personalising PRP therapies. Intra-articular delivery combined with injections in altered ligamentous structures, medial and coronal ligaments or premeniscal pes anserinus showed positive clinical outcomes. Although the evidence supporting these approaches are weak, they merit further consideration to refine PRP protocols and target the right OA phenotypes.

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Intra-articular Injection of Pure Platelet-Rich Plasma Is the Most Effective Treatment for Joint Pain by Modulating Synovial Inflammation and Calcitonin Gene-Related Peptide Expression in a Rat Arthritis Model

Cited by 29 publications

References 42 publications

The Effect of Platelet-Rich Plasma on the Intra-Articular Microenvironment in Knee Osteoarthritis

The Effect of Platelet-Rich Plasma on the Intra-Articular Microenvironment in Knee Osteoarthritis

Osteoarthritis: Novel Molecular Mechanisms Increase Our Understanding of the Disease Pathology

Moving toward targeting the right phenotype with the right platelet-rich plasma (PRP) formulation for knee osteoarthritis

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