Inhibition of fibrotic changes in infrapatellar fat pad alleviates persistent pain and articular cartilage degeneration in monoiodoacetic acid-induced rat arthritis model

An, Jae-Sung; Tsuji, Kunikazu; Onuma, Hiroaki; Araya, Naoko; Isono, Masaaki; Hoshino, Takashi; Inomata, Kei; Hino, Jun; Miyazato, Minoru; Hosoda, Hiroshi; Kangawa, Kenji; Nakagawa, Yusuke; Katagiri, Hiroki; Miyatake, Kazumasa; Sekiya, Ichiro; Muneta, Takeshi; Koga, Hideyuki

doi:10.1016/j.joca.2020.12.014

Cited by 19 publications

(27 citation statements)

References 35 publications

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“…Osteoarthritis (OA) is featured for co-existence of chronic inflammation and cartilage degeneration, and current treatments targeting either aspect are difficult for covering the complex conditions at the same time (Lieberthal et al, 2015). In the middle and late stages of OA progression, neither anti-inflammatory drugs Frontiers in Bioengineering and Biotechnology frontiersin.org nor small molecules that targeting specific molecular target alone cannot fully alleviate the pathological symptoms and prevent the progressive degeneration (An et al, 2021). This study illustrates a therapeutic strategy of the injectable curcumin-loaded PGMs with a dual role of promoting the chondroprotective efficacy under inflammatory conditions and inducing endogenous cartilage regeneration simultaneously.…”

Section: Discussionmentioning

confidence: 99%

Dual role of injectable curcumin-loaded microgels for efficient repair of osteoarthritic cartilage injury

Sun

Wang

et al. 2022

Front. Bioeng. Biotechnol.

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Curcumin has been widely used for the treatment of age-associated diseases, and showed chondroprotective potential for post-traumatic osteoarthritis (OA). However, due to the irregular-shaped and large-sized defects on joint cartilage in degenerated OA, the in vivo delivery and therapeutic effect of curcumin for effective repair remain challenging. In this study, we first present a PEG-GelMA [Poly(Ethylene Glycol) Dimethacrylate-Gelatin Methacrylate, PGMs] hydrogel microgel-based curcumin delivery system for both improved anti-inflammatory and pro-regenerative effects in treatment for cartilage defects. The curcumin-loaded PGMs were produced by a microfluidic system based on light-induced gelation of gelatin methacrylate (GelMA). This PGMs embedding curcumin at a relative low dosage were demonstrated to promote the proliferation and chondrogenic differentiation of mesenchymal stem cells in vitro. More importantly, the PGMs were shown to attenuate the inflammatory response of chondrocytes under IL-1β stimulation. Lastly, the in vivo application of the injectable PGMs significantly promoted the repair of large-sized cartilage injury. These results confirmed that curcumin-loaded PGMs can not only enhance the chondroprotective efficacy under inflammatory conditions but also induce efficient cartilage regeneration. This study provides an advanced strategy with anti-inflammatory and pro-regenerative dual-role therapeutic for treatment of extensive cartilage injuries.

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Section: Discussionmentioning

confidence: 99%

Dual role of injectable curcumin-loaded microgels for efficient repair of osteoarthritic cartilage injury

Sun

Wang

et al. 2022

Front. Bioeng. Biotechnol.

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“…Because low bone density is one of the key clinical features of ACH ( 51 ), the combination a CNP analog and a phosphatase inhibitor could also have a beneficial impact on bone density for patients with ACH and related conditions. In addition, such a treatment could have potential for treatment of osteoporosis and, because CNP/NPR2 also plays a key role in regulation of joint homeostasis, could be beneficial for preventing or minimizing cartilage loss and promoting repair of the damaged articular cartilage in skeletal disorders and osteoarthritis ( 52 ). More generally, the combination of natriuretic peptides and phosphatase inhibitors could have therapeutic potential for multiple disorders involving NPR2 and the related guanylyl cyclase NPR1 that also requires phosphorylation for activity ( 53 ).…”

Section: Discussionmentioning

confidence: 99%

Phosphatase inhibition by LB-100 enhances BMN-111 stimulation of bone growth

Shuhaibar¹,

Kaci²,

Egbert³

et al. 2021

JCI Insight

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Activating mutations in fibroblast growth factor receptor 3 (FGFR3) and inactivating mutations in the natriuretic peptide receptor 2 (NPR2) guanylyl cyclase both result in decreased production of cyclic GMP in chondrocytes and severe short stature, causing achondroplasia (ACH) and acromesomelic dysplasia, type Maroteaux, respectively. Previously, we showed that an NPR2 agonist BMN-111 (vosoritide) increases bone growth in mice mimicking ACH ( Fgfr3 Y367C/+ ). Here, because FGFR3 signaling decreases NPR2 activity by dephosphorylating the NPR2 protein, we tested whether a phosphatase inhibitor (LB-100) could enhance BMN-111–stimulated bone growth in ACH. Measurements of cGMP production in chondrocytes of living tibias, and of NPR2 phosphorylation in primary chondrocytes, showed that LB-100 counteracted FGF-induced dephosphorylation and inactivation of NPR2. In ex vivo experiments with Fgfr3 Y367C/+ mice, the combination of BMN-111 and LB-100 increased bone length and cartilage area, restored chondrocyte terminal differentiation, and increased the proliferative growth plate area, more than BMN-111 alone. The combination treatment also reduced the abnormal elevation of MAP kinase activity in the growth plate of Fgfr3 Y367C/+ mice and improved the skull base anomalies. Our results provide a proof of concept that a phosphatase inhibitor could be used together with an NPR2 agonist to enhance cGMP production as a therapy for ACH.

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“…Targeting fibrotic IFPs by intraarticular injections of C-type natriuretic peptides, inhibited the fibrotic phenotype and subsequently helped to reduce cartilage degeneration and alleviate pain in Wistar rats. 11…”

Section: Anatomical Relationship Between the Ifp And Cartilagementioning

confidence: 99%

“…In a preclinical model of chemically induced IFP fibrosis, histologically evident fibrotic changes of the IFP correlated with cartilage degradation and pain. Targeting fibrotic IFPs by intraarticular injections of C‐type natriuretic peptides, inhibited the fibrotic phenotype and subsequently helped to reduce cartilage degeneration and alleviate pain in Wistar rats 11 …”

Section: Interactions Between the Ifp And Cartilagementioning

confidence: 99%

Source and hub of inflammation: The infrapatellar fat pad and its interactions with articular tissues during knee osteoarthritis

Zhou

Maleitzke

Geißler

et al. 2022

Journal Orthopaedic Research

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Knee osteoarthritis, the most prevalent degenerative joint disorder worldwide, is driven by chronic low‐grade inflammation and subsequent cartilage degradation. Clinical data on the role of the Hoffa or infrapatellar fat pad in knee osteoarthritis are, however, scarce. The infrapatellar fat pad is a richly innervated intracapsular, extrasynovial adipose tissue, and an abundant source of adipokines and proinflammatory and catabolic cytokines, which may contribute to chronic synovial inflammation, cartilage destruction, and subchondral bone remodeling during knee osteoarthritis. How the infrapatellar fat pad interacts with neighboring tissues is poorly understood. Here, we review available literature with regard to the infrapatellar fat pad's interactions with cartilage, synovium, bone, menisci, ligaments, and nervous tissue during the development and progression of knee osteoarthritis. Signaling cascades are described with a focus on immune cell populations, pro‐ and anti‐inflammatory cytokines, adipokines, mesenchymal stromal cells, and molecules derived from conditioned media from the infrapatellar fat pad. Understanding the complex interplay between the infrapatellar fat pad and its neighboring articular tissues may help to better understand and treat the multifactorial pathogenesis of osteoarthritis.

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Inhibition of fibrotic changes in infrapatellar fat pad alleviates persistent pain and articular cartilage degeneration in monoiodoacetic acid-induced rat arthritis model

Cited by 19 publications

References 35 publications

Dual role of injectable curcumin-loaded microgels for efficient repair of osteoarthritic cartilage injury

Dual role of injectable curcumin-loaded microgels for efficient repair of osteoarthritic cartilage injury

Phosphatase inhibition by LB-100 enhances BMN-111 stimulation of bone growth

Source and hub of inflammation: The infrapatellar fat pad and its interactions with articular tissues during knee osteoarthritis

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