BMP‐7 protects against progression of cartilage degeneration after impact injury

Abstract

In vivo studies were used to characterize a model of cartilage injury leading to osteoarthritis progression in the medial femorotibial joint of sheep. In three subsequent studies, bilateral impact injuries were created and one joint received intraarticular injections of 340 mg of rhBMP-7 protein in a collagen particle carrier while the contralateral knee received the vehicle alone. Sheep were allocated to three groups that received intraarticular injections on day 0 (group A), 21 (group B), or 90 (group C) after experimental knee injury. In each group the, joints were evaluated for signs of osteoarthritis progression 90 days after the last treatment using India ink stained area, OARSI histological scoring, cartilage sGAG content, immunostaining for apoptosis (TUNEL), caspase-3, collagen degradation (Col 2 3/4C short collagen epitope), and the endogenous (pro-) form of BMP-7 protein. Knee joints that received rhBMP-7 immediately after injury had small focal lesions at the injury site that did not progress into the surrounding cartilage. Joints that received BMP-7 3 weeks after injury were improved and had limited progression compared to controls, but joints that received the protein 12 weeks after injury had no statistically significant improvement. These studies suggest that BMP-7 may be chondroprotective after traumatic injury in patients if it is administered within 3 to 4 weeks of the index injury. The mechanism of protection after sublethal injury appeared to be an increased survival of chondrocytes that are able to participate in the repair process. ß

Development and Retranslational Validation of anIn VitroModel to Characterize Acute Infections in Large Human Joints

“…Furthermore, the following mediators were included in our analysis; bFGF with its remodeling role in damaged tissue (especially in cartilage) [27, 28], the anabolic and cartilage protective factor IGF-1 and the regenerative factor BMP-7 [29, 30]. As these mediators were concomitantly determined in lavage fluids of acutely infected knee joints, our aim was to determine how reliably the in vivo situation can be reproduced in vitro .…”

Tavşanlarda Artikular Kartilaj Defekt Onarımında Devekuşu Plantar Ligament Kökenli Hücre İçermeyen Matriks Doku Kullanımı

“…Several studies focused on evaluating cartilage repair using different animal models including sheep, horse and goat [13,[27][28][29] . A specialized characteristic of rodents and lagomorphs is that they possess auto-intrinsic repair of cartilage which is not present in larger animal and human [30] .…”

Osteoarthritis: From Palliation to Prevention

“…The ability to observe early and reversible cartilage damage supports development of disease-modifying therapies. Cellular and molecular targets for intervention include administration of chondro-resuscitative substances such as growth factors, anti-apoptotic treatments, free radical scavengers, and anti-inflammatory agents 13,14 . In vitro studies suggest that there is a role for acute treatment after impact injury to articular cartilage when progressive chondrocyte death and apoptosis have been observed within minutes to days 13,15 .…”

“…The transtrochanteric surgical dislocation approach, devised by Ganz et al, is now standard for nondestructive, extensive, open intra-articular hip preservation surgery around the world [40][41][42] . Newer approaches to the hip joint allow surgery to be performed directly on articular cartilage, but biological obstacles to chondral repair remain a strong incentive to correct mechanical problems before irreversible chondral damage occurs 2,13,14,43 . Experience provided by the surgical dislocation approach has facilitated the development of less invasive arthroscopic surgery to address a subset of intra-articular hip disorders that can be safely accessed through percutaneous portals 38,44 .…”