Modeling and Assessing Osteoarthritis in Mice by Destabilization of the Medial Meniscus (DMM).

In this chapter, we describe an induced model of osteoarthritis in mice, frequently employed in the study of this disease. We outline in detail the surgical induction of disease and preparation of samples for histological assessment of disease.

Mechanical forces couple bone matrix mineralization with inhibition of angiogenesis to limit adolescent bone growth.

Bone growth requires a specialised, highly angiogenic blood vessel subtype, so-called type H vessels, which pave the way for osteoblasts surrounding these vessels. At the end of adolescence, type H vessels differentiate into quiescent type L endothelium lacking the capacity to promote bone growth. Until now, the signals that switch off type H vessel identity and thus limit adolescent bone growth have remained ill defined.

Ciliary IFT88 Protects Coordinated Adolescent Growth Plate Ossification From Disruptive Physiological Mechanical Forces.

Compared with our understanding of endochondral ossification, much less is known about the coordinated arrest of growth defined by the narrowing and fusion of the cartilaginous growth plate. Throughout the musculoskeletal system, appropriate cell and tissue responses to mechanical force delineate morphogenesis and ensure lifelong health. It remains unclear how mechanical cues are integrated into many biological programs, including those coordinating the ossification of the adolescent growth plate at the cessation of growth.

Role of Ciliary Protein Intraflagellar Transport Protein 88 in the Regulation of Cartilage Thickness and Osteoarthritis Development in Mice.

Objective: Mechanical and biologic cues drive cellular signaling in cartilage development, health, and disease. Primary cilia proteins, which are implicated in the transduction of biologic and physiochemical signals, control cartilage formation during skeletal development. This study was undertaken to assess the influence of the ciliary protein intraflagellar transport protein 88 (IFT88) on postnatal cartilage from mice with conditional knockout of the Ift88 gene (Ift88-KO).

Comparison of LABORAS with static incapacitance testing for assessing spontaneous pain behaviour in surgically-induced murine osteoarthritis.

Objective: Evoked responses following mechanical or thermal stimulation are typically used to assess pain behaviour in murine osteoarthritis (OA). However, there is no consensus on how best to measure spontaneous pain behaviour.

Method: OA by partial meniscectomy (PMX), or sham surgery was performed in 10-week old C57BL/6 male mice.

TSG-6 Is Weakly Chondroprotective in Murine OA but Does not Account for FGF2-Mediated Joint Protection.

Objective: Tumor necrosis factor α-stimulated gene 6 (TSG-6) is an anti-inflammatory protein highly expressed in osteoarthritis (OA), but its influence on the course of OA is unknown.

Methods: Cartilage injury was assessed by murine hip avulsion or by recutting rested explants. Forty-two previously validated injury genes were quantified by real-time polymerase chain reaction in whole joints following destabilization of the medial meniscus (DMM) (6 hours and 7 days).

Does Pain at an Earlier Stage of Chondropathy Protect Female Mice Against Structural Progression After Surgically Induced Osteoarthritis?

Objective: Female C57BL/6 mice exhibit less severe chondropathy than male mice. This study was undertaken to test the robustness of this observation and explore underlying mechanisms.

Methods: Osteoarthritis was induced in male and female C57BL/6 or DBA/1 mice (n = 6-15 per group) by destabilization of the medial meniscus (DMM) or partial meniscectomy (PMX).

Connective tissue growth factor contributes to joint homeostasis and osteoarthritis severity by controlling the matrix sequestration and activation of latent TGFβ.

Objectives: One mechanism by which cartilage responds to mechanical load is by releasing heparin-bound growth factors from the pericellular matrix (PCM). By proteomic analysis of the PCM, we identified connective tissue growth factor (CTGF) and here investigate its function and mechanism of action.

Methods: Recombinant CTGF (rCTGF) was used to stimulate human chondrocytes for microarray analysis.

Brief Report: JNK-2 Controls Aggrecan Degradation in Murine Articular Cartilage and the Development of Experimental Osteoarthritis.

Objective: The pathogenesis of osteoarthritis (OA) is poorly understood. Loss of the proteoglycan aggrecan from cartilage is an early event. Recently, we identified a role for the JNK pathway, particularly JNK-2, in human articular chondrocytes in vitro in regulating aggrecan degradation.