Parathyroid Hormone-Induced Bone Marrow Mesenchymal Stem Cell Chondrogenic Differentiation and its Repair of Articular Cartilage Injury in Rabbits

Chen, Yushu; Chen, Yi; Zhang, Shujiang; Du, Xiufan; Bai, Bo

doi:10.12659/msmbr.900242

Cited by 16 publications

(14 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For a-c, data represent mean ± SD, n = 4, *P < 0.05, **P < 0.01, ***P < 0.001, and ****P < 0.0001. For d, data represent mean ± SD, n = 6, a single asterisk is used for all levels of significance when P < 0.05 outcomes [18,[20][21][22][23]. In this study, we used a micropellet platform [24] with the aim of generating more definitive insights into how intermittent or constant PTH treatment influenced BMSC chondrogenesis and hypertrophy.…”

Section: Discussionmentioning

confidence: 99%

“…PTH has been explored in BMSC differentiation cultures with varying results. Chen et al reported that PTH-induced rabbit BMSC chondrogenesis resulted in better repair of articular cartilage injury in rabbits, compared with non-PTH-treated BMSC [20]. Zhang et al observed a dose-dependent effect, whereby lower concentrations (1-10 nM) of PTH promoted BMSC chondrogenesis, while higher concentrations (> 100 nM) suppressed matrix production [18].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Intermittent parathyroid hormone (1–34) supplementation of bone marrow stromal cell cultures may inhibit hypertrophy, but at the expense of chondrogenesis

et al. 2020

View full text Add to dashboard Cite

Background: Bone marrow stromal cells (BMSC) have promise in cartilage tissue engineering, but for their potential to be fully realised, the propensity to undergo hypertrophy must be mitigated. The literature contains diverging reports on the effect of parathyroid hormone (PTH) on BMSC differentiation. Cartilage tissue models can be heterogeneous, confounding efforts to improve media formulations. Methods: Herein, we use a novel microwell platform (the Microwell-mesh) to manufacture hundreds of smalldiameter homogeneous micro-pellets and use this high-resolution assay to quantify the influence of constant or intermittent PTH(1-34) medium supplementation on BMSC chondrogenesis and hypertrophy. Micro-pellets were manufactured from 5000 BMSC each and cultured in standard chondrogenic media supplemented with (1) no PTH, (2) intermittent PTH, or (3) constant PTH. Results: Relative to control chondrogenic cultures, BMSC micro-pellets exposed to intermittent PTH had reduced hypertrophic gene expression following 1 week of culture, but this was accompanied by a loss in chondrogenesis by the second week of culture. Constant PTH treatment was detrimental to chondrogenic culture. Conclusions: This study provides further clarity on the role of PTH on chondrogenic differentiation in vitro and suggests that while PTH may mitigate BMSC hypertrophy, it does so at the expense of chondrogenesis.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Intermittent parathyroid hormone (1–34) supplementation of bone marrow stromal cell cultures may inhibit hypertrophy, but at the expense of chondrogenesis

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Parathyroid hormone (PTH) (1-34) inhibits the hypertrophy of BMSCs during chondrogenic differentiation [16,17], inhibits articular cartilage degeneration, and promotes articular chondrocyte proliferation and ECM synthesis [18]. Therefore, it is often used in studies on cartilage tissue engineering as well as in osteoarthritis treatment [19][20][21]. Orth et al [22] reported that injection of PTH (1-34) into a rabbit model of osteochondral defect significantly increased the expression of PTH receptor in chondrocytes and osteocytes in the rabbit joint, improved the surface structure and integration of articular cartilage, and reconstructed the subchondral bone.…”

Section: Discussionmentioning

confidence: 99%

Parathyroid hormone (1-34) promotes the effects of 3D printed scaffold-seeded bone marrow mesenchymal stem cells on meniscus regeneration

Zhao

Zou

Cui

et al. 2020

Preprint

View full text Add to dashboard Cite

Background Cell-based tissue engineering represent a promising management for meniscus repair and regeneration. The present study aimed to investigate whether the injection of parathyroid hormone (PTH) (1–34) could promote the regeneration and chondroprotection of 3D printed scaffold seeded with bone marrow mesenchymal stem cells (BMSCs) in a canine total meniscal meniscectomy model. Methods 3D printed poly(e-caprolactone) scaffold seeded with BMSCs was cultured in vitro, and the effects of in vitro culture time on cell growth and matrix synthesis of the BMSCs-scaffold construct were evaluated by microscopic observation and cartilage matrix content detection at 7, 14, 21, and 28 days. After that, the tissue-engineered meniscus based on BMSCs–scaffold cultured for the appropriate culture time was selected for in vivo implantation. Sixteen dogs were randomly divided into four groups: PTH + BMSCs–scaffold, BMSCs–scaffold, total meniscectomy, and sham operation. The regeneration of the implanted tissue and the degeneration of articular cartilage were assessed by gross, histological, and immunohistochemical analysis at 12 weeks postoperatively. Results In vitro study showed that the glycosaminoglycan (GAG)/DNA ratio and the expression of collagen type II (Col2) were significantly higher on day 21 as compared to the other time points. In vivo study showed that, compared with the BMSCs–scaffold group, the PTH + BMSCs–scaffold group showed better regeneration of the implanted tissue and greater similarity to native meniscus with respect to gross appearance, cells composition, and cartilage extracellular matrix deposition. This group also showed less expression of terminal differentiation markers of BMSC chondrogenesis as well as lower cartilage degeneration with less damage on the knee cartilage surface, higher expression of Col2 and lower expression of degeneration markers. Conclusions Our results demonstrated that PTH (1–34) promotes the regenerative and chondroprotective effects of the BMSCs–3D printed meniscal scaffold in a canine model, and thus their combination could be a promising strategy for meniscus tissue engineering.

show abstract

“…microfractures) or procedures in which an overwhelming concentration of MSCs is combined with chondrocytes, for example during a one-stage cartilage repair procedure. Previous work indeed indicated that PTH-induced rat bone marrow-derived MSCs complexed with fibrin glue effectively promoted repair of a rabbit articular cartilage injury [53]. Stem cells are usually derived from fat or bone marrow [54], but also other cell sources have been proposed, such as human dental pulp stem cells [55] or follicle cells enveloping the dental germ [56].…”

Section: Discussionmentioning

confidence: 99%

PTH decreases in vitro human cartilage regeneration without affecting hypertrophic differentiation

Rutgers¹,

Bach²,

Vonk³

et al. 2019

PLoS ONE

View full text Add to dashboard Cite

Regenerated cartilage formed after Autologous Chondrocyte Implantation may be of suboptimal quality due to postulated hypertrophic changes. Parathyroid hormone-related peptide, containing the parathyroid hormone sequence (PTHrP 1–34), enhances cartilage growth during development and inhibits hypertrophic differentiation of mesenchymal stromal cells (MSCs) and growth plate chondrocytes. This study aims to determine the possible anabolic and/or hypertrophic effect of PTH on human articular chondrocytes. Healthy human articular cartilage-derived chondrocytes (n = 6 donors) were cultured on type II collagen-coated transwells with/without 0.1 or 1.0 μM PTH from day 0, 9, or 21 until the end of culture (day 28). Extracellular matrix production, (pre)hypertrophy and PTH signaling were assessed by RT-qPCR and/or immunohistochemistry for collagen type I, II, X, RUNX2, MMP13, PTHR1 and IHH and by determining glycosaminoglycan production and DNA content. The Bern score assessed cartilage quality by histology. Regardless of the concentration and initiation of supplementation, PTH treatment significantly decreased DNA and glycosaminoglycan content and reduced the Bern score compared with controls. Type I collagen deposition was increased, whereas PTHR1 expression and type II collagen deposition were decreased by PTH supplementation. Expression of the (pre)hypertrophic markers MMP13, RUNX2, IHH and type X collagen were not affected by PTH. In conclusion, PTH supplementation to healthy human articular chondrocytes did not affect hypertrophic differentiation, but negatively influenced cartilage quality, the tissues’ extracellular matrix and cell content. Although PTH may be an effective inhibitor of hypertrophic differentiation in MSC-based cartilage repair, care may be warranted in applying accessory PTH treatment due to its effects on articular chondrocytes.

show abstract

Parathyroid Hormone-Induced Bone Marrow Mesenchymal Stem Cell Chondrogenic Differentiation and its Repair of Articular Cartilage Injury in Rabbits

Cited by 16 publications

References 36 publications

Intermittent parathyroid hormone (1–34) supplementation of bone marrow stromal cell cultures may inhibit hypertrophy, but at the expense of chondrogenesis

Intermittent parathyroid hormone (1–34) supplementation of bone marrow stromal cell cultures may inhibit hypertrophy, but at the expense of chondrogenesis

Parathyroid hormone (1-34) promotes the effects of 3D printed scaffold-seeded bone marrow mesenchymal stem cells on meniscus regeneration

PTH decreases in vitro human cartilage regeneration without affecting hypertrophic differentiation

Contact Info

Product

Resources

About