Future Aspects of Clinical Osteoarthritis Therapies in the Continuum of Translational Research

Schrenker, Steffen; Gao, Liang; Cucchiarini, Magali

doi:10.1055/a-0806-8225

Cited by 3 publications

(6 citation statements)

References 115 publications

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“…It has been associated with heavy physical occupational activities (3,4). If left untreated, hip OA typically leads to chronic pain, decreased quality of life, and various disabilities, and will often require total hip arthroplasty (THA) (5)(6)(7)(8). As the global population ages, THA has become a high-volume surgical intervention for patients with end-stage hip OA (9,10).…”

Section: Introductionmentioning

confidence: 99%

Supercapsular percutaneously-assisted total hip (SuperPath) versus mini-incision posterolateral total hip arthroplasty for hip osteoarthritis: a prospective randomized controlled trial

Meng¹,

Gao²,

Huang³

et al. 2021

Ann Transl Med

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Background: Supercapsular percutaneously-assisted total hip (SuperPath) arthroplasty has been proposed to be minimally invasive and tissue sparing, with possible superior postoperative outcomes compared with conventional approaches for total hip arthroplasty (THA). However, previous studies have underlined the shortcomings of conventional THA approaches, including higher dislocation, more blood loss, longer incisions, more tissue damage, and delayed postoperative rehabilitation. In the present study, we compared the short-term outcomes of unilateral THA with those of SuperPath and the mini-incision posterolateral approach (PLA) for hip osteoarthritis (OA). Methods: Patients with unilateral hip OA were prospectively recruited and underwent either SuperPath (SuperPath group) or mini-incision PLA THA (PLA group). Perioperative status [operative time, incision length, intraoperative blood loss, soft tissue damage, and length of hospital stay (LOS)], and postoperative function outcomes, including range of motion (ROM), pain visual analog scale (VAS), and Harris Hip Score (HHS), were evaluated and compared between the groups at scheduled time points within 12 months postoperatively. Results: Compared with the PLA group, the SuperPath group yielded a significantly shorter incision length (7.83 vs. 12.45 cm, P<0.001), longer operative time (102.72 vs. 66.22 min, P<0.001), more blood loss (1,007.38 vs. 844.55 mL, P=0.005), and more soft tissue damage (creatine kinase: 1,056.05 vs. 821.50 U/L, P=0.006) on postoperative day 3. The SuperPath group also showed deficient acetabular cup positioning (abduction angle: 36.94° vs. 42.66°, P=0.004) and a greater decrease in ROM (flexion: 107.66° vs. 114.44°, P=0.004; 109.83° vs. 116.11°, P=0.002; 111.66° vs. 118.88°, P<0.001) on postoperative days 1, 3, and 14, aswell as severe early-term pain symptoms (pain VAS on postoperative day 3: 7.05 vs. 6.55, P=0.041). However, the LOS, C-reactive protein levels, erythrocyte sedimentation rate (within 2 weeks postoperatively), and HHS were comparable between the groups during the 12 months postoperatively.Conclusions: SuperPath may be a promising, minimally invasive technique for the treatment of OA in the future. Further investigation is necessary to evidence the possible superiority of SuperPath over other conventional mini-incision THA approaches.

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Section: Introductionmentioning

confidence: 99%

Supercapsular percutaneously-assisted total hip (SuperPath) versus mini-incision posterolateral total hip arthroplasty for hip osteoarthritis: a prospective randomized controlled trial

Meng¹,

Gao²,

Huang³

et al. 2021

Ann Transl Med

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“…Die strukturelle Integrität und biochemische Zusammensetzung des hyalinen Knorpels wird durch mechanische und biochemische Reize reguliert. Durch mechanische Überbelastung, proinflammatorische Zytokine, Alterungsprozesse oder genetische Prädisposition kommt es zu einer Änderung der Genexpression in den Chondrozyten mit Ausschüttung proinflammatorischer Zytokine und Matrix degradierender Enzyme [1,2,5]. Diese biochemischen Stressoren verursachen eine Proliferationsaktivität der Chondrozyten mit Produktion knorpelunspezifischer Matrixkomponenten (Kollagen Typ I/X/Osteocalcin) als Zeichen einer gestörten zellulären Homöostase mit zunehmender Verschiebung zu katabolen Signalkaskaden.…”

Section: Pathophysiologie Der Arthroseunclassified

“…Zum anderen besteht ein proinflammtorischer Rückkopplungsmechanismus mit anderen Gewebetypen im betroffenen Gelenk [1,2,7]. Bereits in frühen Arthrosestadien besteht häufig eine Synovialitis mit Proliferation der Synovialzellen, Gewebehypertrophie und vermehrter Vaskularisierung [5]. Neben der Ausschüttung inflammatorischer Mediatoren und Matrixdegradierender Enzyme durch Synovialzellen sinkt die Syntheseleistung an Hyaluronsäure und Lubricin, was die Funktionsfähigkeit des Gelenkes weiter kompromitiert [5,8].…”

Section: Pathophysiologie Der Arthroseunclassified

“…Die kommerziell verfügbaren HAProdukte unterscheiden sich hinsichtlich der HA-Konzentration, des Molekulargewichtes (ca. 500-6000 kDa), und der Anzahl der Injektionen einer Behandlungseinheit (1)(2)(3)(4)(5)…”

Section: Chondroprotektivaunclassified

“…Aus orthopädisch-unfallchirurgischer Sicht stehen zum einen präventive Maßnahmen der operativen Versorgung mechanischer Präarthrosen wie der Hüftdysplasie, des Hüft impingement, der Achsfehlstellungen am Kniegelenk sowie der intraartikulären Verletzungen der Menisci, des vorderen Kreuzbandes und des Gelenkknorpels im Vordergrund [5]. Zum anderen hat das bessere Verständnis molekularbiologischer Prozesse der gestörten Zell-/Gelenkhomöostase und der Inflammation neben den Orthobiologika wie platelet-rich plasma (PRP) neue Strategien der Regenerativen Medizin wie die intraartikuläre Injektion von Zellkonzentraten und mesenchymalen Stammzellen (MSZ) hervorgebracht [6].…”

Section: Introductionunclassified

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Arthroseprävention und mögliche zukünftige Ansätze der Arthrosetherapie – Sicht der Orthopädie und Unfallchirurgie

2020

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ZusammenfassungDie Arthrose wird heute als eine biomechanische und inflammatorische Organerkrankung angesehen. Biomechanisch stehen die angeborenen und erworbenen präarthrotischen Gelenkerkrankungen im Fokus der Erkrankung. Weiterentwicklungen etablierter operativer Verfahren sowie neue entwickelte Techniken haben insbesondere in der Hüft- und Kniegelenkchirurgie dazu beigetragen dem Patienten bessere präventive Therapieoptionen anbieten zu können. Bezüglich der inflammatorischen Komponente hat sich in der letzten Dekade das Feld der regenerativen Therapien mit neuen therapeutischen Ansätzen entwickelt. Die intraartikuläre Applikation von thrombozytenreichen Plasma, Konzentraten aus Knochenmark-/Fettgewebe und ex vivo expandierten mesenchymalen Stammzellen haben erste viel versprechende Ergebnisse gezeigt. Allerdings fehlen bisher aussagekräftige prospektiv-randomisierte klinische Studien. In dieser Arbeit sollen die neuesten Therapieansätze bzgl. der biomechanischen und inflammatorischen Komponenten der Arthrose aus orthopädisch–unfallchirurgischer Sicht dargestellt und diskutiert werden. Desweitern werden neue Ergebnisse etablierter Behandlungsverfahren, wie die Applikation von Chondroprotektiva und Innovationen in der Endoprothetik beleuchtet.

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Designing Nerve Growth Factor Analogues to Suppress Pain Signal Transduction Mediated by the p75NTR-NGF-TrkA Complex: A Structural and Biophysical Perspective

2024

Preprint

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As a key mediator of chronic pain, neurotrophin nerve growth factor (NGF) binds to two neurotrophin receptors: p75 neurotrophin receptor (p75NTR) and tyrosine kinase receptor A (TrkA). The formation of the p75NTR-NGF-TrkA complex is implicated in the potentiation of chronic pain signals, making it an attractive target for therapeutic explorations. NGF analogues and monoclonal antibodies (mAbs) targeting NGF represent two distinct approaches in modulating the intricate signaling pathways involved in pain transduction mediated by the p75NTR-NGF-TrkA complex. While NGF analogues offer the advantage of tailored design to fine-tune neurotrophic responses, monoclonal antibodies provide a more systemic and comprehensive blockade of NGF, inhibiting its interactions with both p75NTR and TrkA receptors. However, the use of mAbs may pose challenges related to potential side effects and interference with the physiological functions of NGF. As a result, balancing the benefits and drawbacks of the two approaches is critical for advancing therapeutic strategies towards the alleviation of p75NTR-NGF-TrkA-mediated pain. In this study, therefore, a novel structural and biophysical approach was employed for the design of NGF analogues to suppress p75NTR-NGF-TrkA-related chronic pain signaling. Employing high-throughput structural modeling and biophysics-based intermolecular binding affinity calculations, this article for the first time puts forward a set of NGF analogues, including in particular NGF analogues with four site-specific mutations, for whose dimerizations the K d at 37 ◦C were reduced by three orders of magnitude (from 10-9 M to 10-6 M) compared to the K d at 37 ◦C for the dimerization of native NGFs. Overall, the integration of structural and biophysical perspectives enhances our understanding of the rational design of NGF analogues as promising candidates for the development of NGF-targeted analgesic therapies, which balances the benefits and drawbacks of anti-NGF antibodies and NGF analogues for advancing therapeutic strategies towards the alleviation of p75NTR-NGF-TrkA-mediated pain.

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Future Aspects of Clinical Osteoarthritis Therapies in the Continuum of Translational Research

Cited by 3 publications

References 115 publications

Supercapsular percutaneously-assisted total hip (SuperPath) versus mini-incision posterolateral total hip arthroplasty for hip osteoarthritis: a prospective randomized controlled trial

Supercapsular percutaneously-assisted total hip (SuperPath) versus mini-incision posterolateral total hip arthroplasty for hip osteoarthritis: a prospective randomized controlled trial

Arthroseprävention und mögliche zukünftige Ansätze der Arthrosetherapie – Sicht der Orthopädie und Unfallchirurgie

Designing Nerve Growth Factor Analogues to Suppress Pain Signal Transduction Mediated by the p75NTR-NGF-TrkA Complex: A Structural and Biophysical Perspective

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