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. 2017 Jun;45(7):1512-1521.
doi: 10.1177/0363546516686965. Epub 2017 Jan 27.

V体育官网 - Intra-articular Recombinant Human Proteoglycan 4 Mitigates Cartilage Damage After Destabilization of the Medial Meniscus in the Yucatan Minipig

Kimberly A Waller  1 , Kaitlyn E Chin  1 , Gregory D Jay  2   3 , Ling X Zhang  2 , Erin Teeple  4   5 , Scott McAllister  1 , Gary J Badger  6 , Tannin A Schmidt  7 , Braden C Fleming  1   3
Affiliations

Intra-articular Recombinant Human Proteoglycan 4 Mitigates Cartilage Damage After Destabilization of the Medial Meniscus in the Yucatan Minipig

"V体育官网入口" Kimberly A Waller et al. Am J Sports Med. 2017 Jun.

Abstract

Background: Lubricin, or proteoglycan 4 (PRG4), is a glycoprotein responsible for joint boundary lubrication. PRG4 has been shown previously to be down-regulated after traumatic joint injury such as a meniscal tear VSports手机版. Preliminary evidence suggests that intra-articular injection of PRG4 after injury will reduce cartilage damage in rat models of surgically induced posttraumatic osteoarthritis. .

Objective: To determine the efficacy of intra-articular injection of full-length recombinant human lubricin (rhPRG4) for reducing cartilage damage after medial meniscal destabilization (DMM) in a preclinical large animal model V体育安卓版. .

Study design: Controlled laboratory study. V体育ios版.

Methods: Unilateral DMM was performed in 29 Yucatan minipigs. One week after DMM, animals received 3 weekly intra-articular injections (3 mL per injection): (1) rhPRG4 (1. 3 mg/mL; n = 10); (2) rhPRG4+hyaluronan (1. 3 mg/mL rhPRG4 and 3 mg/mL hyaluronan [~950 kDA]; n = 10); and (3) phosphate-buffered saline (PBS; n = 9). Hindlimbs were harvested 26 weeks after surgery. Cartilage integrity was evaluated by use of macroscopic (India ink) and microscopic (safranin O-fast green and hematoxylin and eosin) scoring systems VSports最新版本. Secondary outcomes evaluated via enzyme-linked immunosorbent assay (ELISA) included PRG4 levels in synovial fluid, carboxy-terminal telepeptide of type II collagen (CTX-II) concentrations in urine and serum, and interleukin 1β (IL-1β) levels in synovial fluid and serum. .

Results: The rhPRG4 group had significantly less macroscopic cartilage damage in the medial tibial plateau compared with the PBS group ( P = . 002). No difference was found between the rhPRG4+hyaluronan and PBS groups ( P = . 23). However, no differences in microscopic damage scores were observed between the 3 groups ( P = . 70). PRG4 production was elevated in the rhPRG4 group synovial fluid compared with the PBS group ( P = . 033). The rhPRG4 group presented significantly lower urinary CTX-II levels, but not serum levels, when compared with the PBS ( P = . 013) and rhPRG4+hyaluronan ( P = V体育平台登录. 011) groups. In serum and synovial fluid, both rhPRG4 ( P = . 006; P = . 017) and rhPRG4+hyaluronan groups ( P = . 009; P = . 03) presented decreased IL-1β levels. .

Conclusion: All groups exhibited significant cartilage degeneration after DMM surgery. However, animals treated with rhPRG4 had the least amount of cartilage damage and less inflammation, providing evidence that intra-articular injections of rhPRG4 may slow the progression of posttraumatic osteoarthritis. VSports注册入口.

Clinical relevance: Patients with meniscal trauma are at high risk for posttraumatic osteoarthritis. This study demonstrates that an intra-articular injection regimen of rhPRG4 may attenuate cartilage damage after meniscal injury. V体育官网入口.

Keywords: PRG4; hyaluronan; inflammation; lubricin; meniscus; osteoarthritis. VSports在线直播.

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Figures

1
1
Macroscopic Cartilage Assessment for the medial tibial plateau (MTP). a) Images from the median lesion severity score for each treatment group: rhPRG4, rhPRG4+HA, and PBS. b) India ink scoring revealed significantly lower medial tibial plateau scores in the rhPRG4 group compared to the PBS group (p=.002). Error bars represent the standard deviations.
2
2
Histological images the median medial tibial plateau from the mid-coronal plane stained with H&E (top row) and Safranin O-fast green (bottom row). Scale bar is 500μm.
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3
Mean histological sub-scores for the three treatment groups. A) Structure (p=.78), B) Chondrocyte Density (p=.93), C) Cell Cloning (p=.45), and D) Glycosaminoglycan staining (p=.26). There were no significant differences between groups. Error bars represent the standard deviations.
4
4
Elevated levels of PRG4 levels were present in the synovial fluid of the rhPRG4 treated limbs compared to the PBS treated limbs (p=.033). There was no significant difference between the rhPRG4 group and the rhPRG4+hyaluronan group (p=0.17) or between the rhPRG4+HA and PBS group (p=.09). Error bars represent the standard deviations.
5
5
CTX-II concentrations. a) Urinary CTX-II levels normalized by creatinine. rhPRG4 treated joints exhibited reduced urinary CTX-II levels compared to PBS and rhPRG4+HA treated joints (p=.013 and .011, respectively). b) CTX-II levels in the serum were not significant between treatment groups (p=.94). Error bars represent the standard deviations.
6
6
IL-1β concentrations. a) Serum IL-1β concentration was also reduced in the rhPRG4 and rhPRG4+HA groups compared to the PBS group (p=.006; p=.009). b) The synovial fluid IL-1β concentration was diminished in the rhPRG4 and rhPRG4+HA groups compared to the PBS group (p=.017; p=.029). There was no significant difference between the rhPRG4 group and the rhPRG4+hyaluronan group (p=.81). Error bars represent the standard deviations.
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"VSports手机版" References

    1. Abubacker S, Dorosz SG, Ponjevic D, Jay GD, Matyas JR, Schmidt TA. Full-Length Recombinant Human Proteoglycan 4 Interacts with Hyaluronan to Provide Cartilage Boundary Lubrication. Ann Biomed Eng. 2016;44:1128–1137. - PubMed
    1. Ai M, Cui Y, Sy MS, et al. Anti-lubricin monoclonal antibodies created using lubricin-knockout mice immunodetect lubricin in several species and in patients with healthy and diseased joints. PLoS One. 2015;10:e0116237. - PMC - PubMed
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    1. Atarod M, Ludwig TE, Frank CB, Schmidt TA, Shrive NG. Cartilage boundary lubrication of ovine synovial fluid following anterior cruciate ligament transection: a longitudinal study. Osteoarthritis Cartilage. 2015;23:640–647. - PubMed

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