Chunyi Wen

FABP4 as a biomarker for knee osteoarthritis

AIMnTo explore the role of an adipokine-termed fatty acid-binding protein 4 (FABP4) in osteoarthritis (OA).nnnMETHODSnPatients with primary knee OA and non-OA controls were included. Paired tissues including plasma, synovial fluid (SF), subcutaneous fat and infrapatellar fat pad (IPFP) were harvested during surgery. FABP4 concentration was determined by ELISA.nnnRESULTSnPlasma FABP4 increased significantly with OA stage (nxa0=xa0263). OA patients (nxa0=xa038) had significantly higher plasma and SF FABP4 than non-OA patients (nxa0=xa029). FABP4 level of IPFP was positively correlated with SF FABP4.nnnCONCLUSIONnOA patients had significantly high systemic and local FABP4, and IPFP may be the main source of FABP4 in synovial cavity. FABP4 may be a promising biomarker for OA.

Spontaneous hypertensive rat exhibits bone and meniscus phenotypes of osteoarthritis: is it an appropriate control for MetS-associated OA?

The potential roles of metabolic syndrome (MetS) in the onset and progression of osteoarthritis (OA) have been a hot topic in the field since it may potentially open up to new non-surgical treatment regimens. To better study the relationship between MetS and OA, a suitable animal model would be a vital tool in understanding the pathomechanism and also for screening and testing various potential drug candidates.nnWe have recently read Deng and colleagues’ letter entitled ‘Eplerenone treatment alleviates the development of joint lesions in a new rat model of spontaneous metabolic-associated osteoarthritis’ published online this May, which mentioned the use of ‘obese spontaneously hypertensive heart failure’ (SHHFcp/cp) rat model to study MetS-associated OA and chronic administration of eplerenone, a mineralocorticoid receptor antagonist, as a treatment.1 While we appreciate the authors’ dedicated effort, we believe there are several …

Do immune cells lead the way in subchondral bone disturbance in osteoarthritis

Osteoarthritis (OA) is a whole-joint disorder, and non-cartilage articular pathologies, e.g. subchondral bone disturbance, contribute substantially to the onset and progression of the disease. In the early stage of OA, abnormal mechanical loading leads to micro-cracks or micro-fractures that trigger a reparative process with angiogenesis and inflammatory response. With the progression of disease, cystic lesion, sclerosis and osteophytosis occur at tissue level, and osteoblast dysfunction at cellular level. Osteoblasts derived from OA sclerotic bone produce increased amount of type I collagen with aberrant Col1A1/A2 ratio and poor mineralization capability. The coupling mechanism of bone resorption with formation is also impaired with elevated osteoclastic activities. All these suggest a view that OA subchondral bone presents a defective fracture repair process in a chronic course. It has been found that T and B cells, the major effectors in the adaptive immunity, take part in the hard callus formation at fracture site in addition to the initial phase of haematoma and inflammation. Infiltration of lymphocytes could interplay with osteoclasts and osteoblasts via a direct physical cell-to-cell contact. Several lines of evidence have consistently shown the involvement of T and B cells in osteoclastogenesis and bone erosion in arthritic joints. Yet the biological link between immune cells and osteoblastic function remains ambiguous. This review will discuss the current knowledge regarding the role of immune cells in bone remodelling, and address its implications in emerging basic and clinical investigations into the pathogenesis and management of subchondral bone pathologies in OA.

High-Frequency Ultrasound Imaging of Tidemark In Vitro in Advanced Knee Osteoarthritis

High-frequency ultrasound imaging has been widely adopted for assessment of the degenerative changes of articular cartilage in osteoarthritis (OA). Yet, there are few reports on investigating its capability to evaluate subchondral bone. Here, we employed high-frequency ultrasound imaging (25u2009MHz) to examine in vitro the tidemark in cylindrical osteochondral disks (nu2009=u200933) harvested from advanced OA knees of humans. We found good correspondence in morphology observed by ultrasound imaging and micro-computed tomography. Ultrasound roughness index (URI) of tidemark was derived from the raw radiofrequency signals to compare with bone quality factors, including bone volume fraction (BV/TV) and bone mineral density (BMD) measured by micro-computed tomography, using the Spearman correlation (ρ). URI of the tidemark was negatively associated with the subchondral plate BV/TV (ρu2009=u2009-0.73, pu2009<0.001), BMD (ρu2009=u2009-0.40, pu2009=u20090.020), as well as the underneath trabecular bone BV/TV (ρu2009=u2009-0.39, pu2009=u20090.025) and BMD (ρu2009=u2009-0.43, pu2009=u20090.012). In conclusion, this preliminary study demonstrated that morphology measured by high-frequency ultrasound imaging could reflect the quality of the subchondral bone. High-frequency ultrasound is a promising imaging tool to evaluate the changes of the subchondral bone in addition to those of the overlying cartilage in OA.

Photoacoustic imaging of synovial tissue hypoxia in experimental post-traumatic osteoarthritis

OBJECTIVESnThis pilot study aimed to investigate the feasibility of non-invasively assessing synovial tissue hypoxia inxa0vivo using photoacoustic (PA) imaging in a post-traumatic osteoarthritis model and explore its correlation with OA severity.nnnMETHODSnThe three-dimensional vasculature structure and oxygenation level of synovial tissues of destabilization of the medial meniscus (DMM)-induced osteoarthritis (OA) mice were longitudinally monitored using PA imaging. Vascular volume/tissue volume (%) and tissue oxygen saturation (sO2) were validated against results obtained by established Power Doppler (PD) imaging and dynamic changes of inhaled O2 concentration respectively. PA changes were correlated with the histological grading of cartilage damages.nnnRESULTSnPA-measurements of vascularity and sO2 demonstrated a strong correlation with localized blood flow detected by PD imaging (ru202f=u202f0.506, pu202f<u202f0.001) and inhaled O2 concentration. DMM knees exhibited much more vascularity in synovial tissue at 4 months after surgery (median 11.3%, IQR: 10.7-15.5%) than the intact knees at time zero (median:5.1%, IQR:3.8-6.8%, pu202f<u202f0.001) as well as the sham-operated knees (median: 4%, IQR: 3.75-5.45%, pu202f=u202f0.017). Paradoxically, synovial tissue sO2 was significantly lower in DDM knees (median: 37.7%, IQR: 36.4-40.6%) than both the intact (47.1%, IQR: 41.9-49.8% pu202f=u202f0.001) and sham-operated knees (45.1% IQR: 45.1-52.4%, pu202f=u202f0.017). The PA-detected synovial tissue hypoxia correlated with the severity of cartilage loss in DMM mice (rhou202f=u202f-0.597, pu202f=u202f0.031).nnnCONCLUSIONnHere, we demonstrated PA imaging can be implemented for non-invasive imaging of the synovial tissue. Under PA imaging, synovitis in OA was characterized by increased angiogenesis and synovial tissue hypoxia; the latter was associated with the severity of OA.

In-vivo three-dimensional optoacoustic molecular imaging of the synovial vasculature in a mouse model of knee joint osteoarthritis (Conference Presentation)

Synovitis is a driver of osteoarthritis. Imaging of the synovial vasculature is essential for osteoarthritis assessment, while traditional imaging techniques like contrast-enhanced MRI/CT and conventional ultrasonography have limitations such as invasive manipulation, radiation and subjective results. In this study, an emerging non-invasive ultrasound imaging technique – optoacoustic molecular imaging (OA) was applied to evaluate the synovial vasculature in a mouse model of knee joint osteoarthritis. 16 male Balb/c mice undertook destabilization of medial meniscus surgery (DMM), 8 were intact as baseline controls. Three-dimensional high-frequency ultrasonography, including B mode, Power Doppler (PD) and OA, was performed to the knees of live mice at baseline (n=8), 1 month (n=8), and 4 months (n=7) after DMM, before tissue harvest. We found that OA vascular density increased significantly at 1 month (p=0.028) and remained high at 4 months (p=0.541), indicating synovial neovascularization during osteoarthritis progression, which was consistent with uCT-based angiography and histological findings. Meanwhile, OA could also evaluate the function of the synovial vasculature by measuring blood oxygen saturation (sO2). We found OA sO2 declined significantly at 4 months compared to baseline (p=0.043) and 1 month (p=0.027), indicating vascular dysfunction at late stage osteoarthritis. Moreover, OA sO2 was found closely related with histological cartilage damage (p=0.028). In this study, we demonstrated that OA was reliable to evaluate the small vasculatures in the knee joint of DMM mouse model. Our findings provided a new technique for the non-invasive monitoring of both structure and function of the synovial vasculature during osteoarthritis progression.

Is subchondral bone cyst formation in non-load-bearing region of osteoarthritic knee a vascular problem?

Subchondral bone cyst is common in the progressive knee osteoarthritis yet its underlying mechanism remains unclear. In addition to the existing theories such as synovial fluid influx and mechanical contusion, we identified the potential link between vascular pathology and osteoarthritic bone pathologies including cystic lesion formation, particularly in the non-load-bearing region. This new hypothesis for SBC formation in non-load-bearing region for knee, which cannot be explained by the existing theories, will provide us a new angle to understand the pathomechanism and pathophysiology of subchondral bone disturbance in osteoarthritis in addition to the classical biomechanical overloading theories. It might guide us to develop a novel diagnostic and therapeutic approach to treat progressive osteoarthritis via targeting vascular pathology.

Serum Osteocalcin and Testosterone Concentrations in Adult Males with or without Primary Osteoporosis: A Meta-Analysis

Osteocalcin (Ocn) and testosterone play important roles in male skeleton. However, the concentrations of serum osteocalcin and testosterone have never been systematically compared between populations with and without primary male osteoporosis, a common skeletal disorder in adult males. We searched the PubMed, Embase, and Cochrane Library for relevant studies. A meta-analysis was performed to compare the serum osteocalcin and testosterone concentrations between primary osteoporotic males and age-matched nonosteoporotic (non-OP) males. Five case-control studies with 300 adult males were included. We found no significant difference between cases and controls in serum total osteocalcin (TOcn) [95% confidence interval (CI): −1.25, 1.31; p = 0.96] and total testosterone (TT) concentrations [95% CI: −0.88, 4.22; p = 0.20]. The level of evidence of this carefully performed meta-analysis is 3a according to Oxford (UK) CEBM Levels of Evidence. Future well-designed studies with larger sample size and better standardization of Ocn assay are awaited to confirm and update our current findings.