scholarly journals Dynamic Compressive Loading Enhances Cartilage Matrix Synthesis and Distribution and Suppresses Hypertrophy in hMSC-Laden Hyaluronic Acid Hydrogels

2012 ◽  
Vol 18 (7-8) ◽  
pp. 715-724 ◽  
Author(s):  
Liming Bian ◽  
David Y. Zhai ◽  
Emily C. Zhang ◽  
Robert L. Mauck ◽  
Jason A. Burdick
Author(s):  
Liming Bian ◽  
Robert L. Mauck ◽  
Jason A. Burdick

While hyaluronic acid (HA) hydrogels provide a stable 3D environment that is conducive to the chondrogenesis of mesenchymal stem cells (MSCs) in the presence of growth factors [1], the neocartilage that is formed remains inferior to native tissue, even after long culture durations. Additionally, MSCs eventually transit into a hypertrophic phenotype after chondrogenic induction, resulting in the calcification of the ECM after ectopic transplantation [2]. From a material design perspective, variation in the HA hydrogel scaffold crosslinking density via changes in the HA macromer concentration can influence chondrogenesis of MSCs and neocartilage formation [3]. Recent studies have also demonstrated that dynamic compression enhances the expression of chondrogenic markers and cartilage matrix synthesis by MSCs encapsulated in various hydrogels, including agarose [4], alginate [5] and fibrin [6]. Furthermore, mechanical signals also regulate growth plate and articular cartilage chondrocyte hypertrophy via the IHH-PTHrP (India hedgehog, Parathyroid hormone-related protein) pathway [7]. In contrast to biologically inert scaffold materials, HA is capable of interacting with cells (including MSCs) via cell surface receptors (CD44, CD54, and CD168) [8; 9]. Therefore the objectives of this study were to (i) evaluate the effects of both hydrogel crosslinking and dynamic compressive loading on (i) chondrogenesis and cartilage matrix production/distribution of human MSCs encapsulated in HA gels and (ii) hypertrophic differentiation of human MSCs using an in vitro MSC hypertrophy model [10].


2013 ◽  
Vol 19 (9-10) ◽  
pp. 1199-1208 ◽  
Author(s):  
Peihui Wu ◽  
Elizabeth DeLassus ◽  
Debabrata Patra ◽  
Weiming Liao ◽  
Linda J. Sandell

2021 ◽  
Vol 12 ◽  
Author(s):  
Yuchen He ◽  
Lauren Yocum ◽  
Peter G Alexander ◽  
Michael J Jurczak ◽  
Hang Lin

Physiological mechanical stimulation has been shown to promote chondrogenesis, but excessive mechanical loading results in cartilage degradation. Currently, the underlying mechanotransduction pathways in the context of physiological and injurious loading are not fully understood. In this study, we aim to identify the critical factors that dictate chondrocyte response to mechanical overloading, as well as to develop therapeutics that protect chondrocytes from mechanical injuries. Specifically, human chondrocytes were loaded in hyaluronic hydrogel and then subjected to dynamic compressive loading under 5% (DL-5% group) or 25% strain (DL-25% group). Compared to static culture and DL-5%, DL-25% reduced cartilage matrix formation from chondrocytes, which was accompanied by the increased senescence level, as revealed by higher expression of p21, p53, and senescence-associated beta-galactosidase (SA-β-Gal). Interestingly, mitophagy was suppressed by DL-25%, suggesting a possible role for the restoration mitophagy in reducing cartilage degeneration with mechanical overloading. Next, we treated the mechanically overloaded samples (DL-25%) with Urolithin A (UA), a natural metabolite previously shown to enhance mitophagy in other cell types. qRT-PCR, histology, and immunostaining results confirmed that UA treatment significantly increased the quantity and quality of cartilage matrix deposition. Interestingly, UA also suppressed the senescence level induced by mechanical overloading, demonstrating its senomorphic potential. Mechanistic analysis confirmed that UA functioned partially by enhancing mitophagy. In summary, our results show that mechanical overloading results in cartilage degradation partially through the impairment of mitophagy. This study also identifies UA’s novel use as a compound that can protect chondrocytes from mechanical injuries, supporting high-quality cartilage formation/maintenance.


Vacuum ◽  
2021 ◽  
pp. 110323
Author(s):  
Faisal Nazeer ◽  
Syed Zohaib Hassan Naqvi ◽  
Abul Kalam ◽  
A.G. Al-Sehemi ◽  
Hussein Alrobi

2012 ◽  
Vol 3 (2) ◽  
pp. 101-117
Author(s):  
Luiz Antônio Bragança da Cunda ◽  
Branca Freitas de Oliveira ◽  
Guillermo Juan Creus

1988 ◽  
Vol 90 (4) ◽  
pp. 635-643 ◽  
Author(s):  
C.A. Poole ◽  
S. Ayad ◽  
J.R. Schofield

A heterogenous population of intact chondrons extracted from low-speed homogenates of canine tibial cartilage were stained by indirect immunofluorescence methods with a polyclonal antibody to type VI collagen. In each of the four chondron groups examined, anti-(type VI collagen) anti-serum was concentrated in the capsule immediately adjacent to the chondrocyte complex. A constant but weaker fluorescent reaction persists in ‘tail-like’ extensions common to single and double chondrons and in the medial connections between adjacent chondrons in linear columns and aggregated clusters. Frayed collagen bundles typical of chondron preparations did not react with the antibody. Similarly, chondrons reacted with normal rabbit serum, or treated by type VI collagen extraction procedures, showed no staining reaction. The differential localization of type VI collagen in the pericellular capsule is discussed in relation to the maintenance of the chondron's integrity and to the protection of the chondrocyte during dynamic compressive loading.


2009 ◽  
Vol 102 (3) ◽  
pp. 948-959 ◽  
Author(s):  
G.D. Nicodemus ◽  
K.A. Shiplet ◽  
S.R. Kaltz ◽  
S.J. Bryant

Sign in / Sign up

Export Citation Format

Share Document