Cartilage morphogenetic proteins: role in joint development, homoeostasis, and regeneration

Abstract

Background: Articular cartilage homoeostasis is critical for joint function. The steady state homoeostasis of articular cartilage is a balance between anabolic morphogens such as cartilage derived morphogenetic proteins (CDMPs) and bone morphogenetic proteins (BMPs) of the BMP family and catabolic cytokines such as interleukin (IL)1, IL17, and tumour necrosis factor α. Although bone and articular cartilage are adjacent tissues, there is a profound difference in their regeneration potential. Bone has the highest potential for regeneration. On the other hand, articular cartilage is recalcitrant to repair. Objective: To examine the hypothesis that the feeble innate regeneration ability of cartilage is due to the preponderance of catabolic cytokines such as IL1 and IL17. Results: During a systematic investigation of CDMPs and cytokines IL17B (chondroleukin) was found in bovine articular cartilage. Discussion and conclusions: BMP-7 and IL17B are present in articular cartilage and synthesised in chondrocytes as shown by northern blots and real-time reverse transcription-polymerase chain reaction. The coexistence of anabolic morphogens and catabolic cytokines in articular cartilage has important implications for cartilage homoeostasis and regeneration. The networks of signalling systems of morphogens and cytokines determine the net capacity for regenerative morphogenesis of articular cartilage. Finally, the feeble innate capacity for articular cartilage may be improved by targeted therapy by soluble receptors to block catabolic cytokines.

Differential regulation of lubricin/superficial zone protein by transforming growth factor β/bone morphogenetic protein superfamily members in articular chondrocytes and synoviocytes

“…Mouse GDF-5 is a homolog of human cartilage-derived morphogenetic protein 1, and is closely related to the BMP subgroups BMP-2/ BMP-4 and BMP-5/BMP-6/BMP-7 (28). Although its essential role in the formation of cartilaginous tissue during embryonic limb development has been demonstrated (41,(44)(45)(46), its role in articular cartilage is not fully understood. There are 3 isoforms of activins: activin A, activin B, and activin AB.…”

“…TGF␤ is an important anabolic factor in articular cartilage (29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40). BMPs are related to TGF␤ and have fundamental roles in the initiation and maintenance of articular cartilage (41)(42)(43). Mouse GDF-5 is a homolog of human cartilage-derived morphogenetic protein 1, and is closely related to the BMP subgroups BMP-2/ BMP-4 and BMP-5/BMP-6/BMP-7 (28).…”

Regeneration Mechanism of Full Thickness Cartilage Defect Using Combination of Freeze Dried Bovine Cartilage Scaffold - Allogenic Bone Marrow Mesenchymal Stem Cells - Platelet Rich Plasma Composite (SMPC) Implantation

“…Freeze Dried Bovine Cartilage Powder (FDBC) contains extracellular matrix and able to stimulate chondrogenesis such as CDMP1/GDF5 [13]. MSC-scaffold combination mixed with platelet rich plasma contains various growth factors.…”

Regulation of the friction coefficient of articular cartilage by TGF‐β1 and IL‐1β

“…1 Lubrication of these surfaces is critical to normal joint function. A boundary lubricant of articular cartilage, referred to as superficial zone protein (SZP), has been identified as a product of the proteoglycan 4 gene (PRG4).…”

“…14 A model of cartilage homeostasis involves the steady-state maintenance of the tissue and the interplay between mechanical and biochemical environmental signals, such as cytokines and their interactions with cells and surrounding extracellular matrix. 1 With reference to cytokines, cartilage homeostasis has been modeled as the balance between the actions of morphogens and growth factors, such as transforming growth factors (TGF-b), bone morphogenetic proteins, and insulin-like growth factor, and the actions of catabolic cytokines, such as interleukins (IL-1b) and tumor necrosis factor alpha. Introduction of inflammatory (catabolic) cytokines, such as IL-1b, to the articular joint reduces the production of matrix molecules and leads to changes in matrix constitution that result in reduced mechanical strength and ability to maintain normal cartilage function.…”