Regulation of lubricin for functional cartilage tissue regeneration: a review

Abstract

Background: Lubricin is chondrocyte-secreted glycoprotein that primarily conducts boundary lubrication between joint surfaces. Besides its cytoprotective function and extracellular matrix (ECM) attachment, lubricin is recommended as a novel biotherapeutic protein that restore functional articular cartilage. Likewise, malfunction of lubrication in damaged articular cartilage caused by complex and multifaceted matter is a major concern in the field of cartilage tissue engineering.

Main body: Although a noticeable progress has been made toward cartilage tissue regeneration through numerous approaches such as autologous chondrocyte implantation, osteochondral grafts, and microfracture technique, the functionality of engineered cartilage is a challenge for complete reconstruction of cartilage. Thus, delicate modulation of lubricin along with cell/scaffold application will expand the research on cartilage tissue engineering.

Conclusion: In this review, we will discuss the empirical analysis of lubricin from fundamental interpretation to the practical design of gene expression regulation.

Keywords: Articular cartilage; ECM; Lubricin; Superficial zone protein (SZP); Tissue engineering.

Fig. 1

Articular cartilage structure with the illustration of collagen fiber orientation [43]

Fig. 2

Schematic representations of (a) lubricin and (b-c) bottle-brush polymers mimicking lubricin [42]

Fig. 3

Effect of synthesized aqueous lubricants on coefficient of friction (COF) with NBrMGs, SB-g-PNIPAAm, and SB-g-NBrMGs (a) of different concentration under the normal load of 5 N at 25 °C (b) under different loads (c) under the normal load of 5 N at different temperature (d) schematic diagram illustrating the hydrophilicity/hydrophobicity transition of NBrMGs and SB-g-NBrMGs around the volume phase transition temperature (VPTT) [56]

Fig. 4

a and b, Effects of bone morphogenetic protein (BMP) family members on SZP accumulation in superficial zone articular chondrocytes (a) and synoviocytes (b). Primary superficial zone articular chondrocytes and synoviocytes were cultured for 3 days as monolayers in serum-free chemically defined medium with or without the addition of BMPs or growth differentiation factor 5 (GDF-5). SZP accumulation in the culture medium was quantified by enzyme-linked immunosorbent assay. Responses to BMPs were much higher in synoviocytes than in chondrocytes. * = P < 0.05; ** = P < 0.01, versus control. C and D, Effects of concurrent treatment with TGFβ1 (1 ng/ml) and BMPs (100 ng/ml) on SZP accumulation in superficial zone articular chondrocytes (c) and synoviocytes (d). SZP accumulation with the combined treatment was significantly higher than that observed with each treatment alone (P < 0.05), and the additive action was seen in both superficial zone articular chondrocytes and synoviocytes. Values are the mean and SEM from 7 individual experiments, each with cartilage from a different animal. T + B2 = TGFβ1 plus BMP-2; T + B4 = TGFβ1 plus BMP-4; T + B7 = TGFβ1 plus BMP-7; T + G5 = TGFβ1 plus GDF-5 [82]