Infrapatellar fat pad adipose tissue-derived macrophages display a predominant CD11c+CD206+ phenotype and express genotypes attributable to key features of OA pathogenesis.

Objectives: In knee osteoarthritis (OA), macrophages are the most predominant immune cells that infiltrate synovial tissues and infrapatellar fat pads (IPFPs). Both M1 and M2 macrophages have been described, but their role in OA has not been fully investigated. Therefore, we investigated macrophage subpopulations in IPFPs and synovial tissues of knee OA patients and their correlation with disease severity, examined their transcriptomics, and tested for factors that influenced their polarization. Methods: Synovial tissues and IPFPs were obtained from knee OA patients undergoing total knee arthroplasty. Macrophages isolated from these joint tissues were characterized via flow cytometry. Transcriptomic profiling of each macrophage subpopulations was performed using NanoString technology. Peripheral blood monocyte-derived macrophages (MDMs) were treated with synovial fluid and synovial tissue- and IPFP-conditioned media. Synovial fluid-treated MDMs were treated with platelet-rich plasma (PRP) and its effects on macrophage polarization were observed. Results: Our findings show that CD11c+CD206+ macrophages were predominant in IPFPs and synovial tissues compared to other macrophage subpopulations (CD11c+CD206-, CD11c-CD206+, and CD11c-CD206- macrophages) of knee OA patients. The abundance of macrophages in IPFPs reflected those in synovial tissues but did not correlate with disease severity as determined from Mankin scoring of cartilage destruction. Our transcriptomics data demonstrated highly expressed genes that were related to OA pathogenesis in CD11c+CD206+ macrophages than CD11c+CD206-, CD11c-CD206+, and CD11c-CD206- macrophages. In addition, MDMs treated with synovial fluid, synovial tissue-conditioned media, or IPFP-conditioned media resulted in different polarization profiles of MDMs. IPFP-conditioned media induced increases in CD86+CD206+ MDMs, whereas synovial tissue-conditioned media induced increases in CD86+CD206- MDMs. Synovial fluid treatment (at 1:8 dilution) induced a very subtle polarization in each macrophage subpopulation. PRP was able to shift macrophage subpopulations and partially reverse the profiles of synovial fluid-treated MDMs. Conclusion: Our study provides an insight on the phenotypes and genotypes of macrophages found in IPFPs and synovial tissues of knee OA patients. We also show that the microenvironment plays a role in driving macrophages to polarize differently and shifting macrophage profiles can be reversed by PRP.

Histological features of knee osteoarthritis treated with triamcinolone acetonide and hyaluronic acid.

Osteoarthritis (OA) is one of the most common degenerative joint diseases leading to disability in the end stage. Although intra-articular triamcinolone acetonide (TA) is one of the OA treatments that have been widely used, the side effects of such corticosteroids are still controversial. Intra-articular hyaluronic acid (HA) injection is another therapeutic option for patients with OA who do not want to use corticosteroids because of their side effects. However, the difference between the histological features associated with TA and HA in the treatment of OA remains unclear. Thus, the present study aimed to compare the histological effects of TA and HA on the cartilage of patients with knee OA. In the current study, 31 patients diagnosed with grade 3-4 knee OA on the Kellgren-Lawrence radiographic grading scale were separated into three groups: TA (n=12); HA (n=7) and untreated group (n=12). Histological examination of the whole articular cartilages of the patients was performed with hematoxylin and eosin and Alcian staining, as well as using a TUNEL assay. Clinical data such as cartilage thickness, structural and component deterioration, proteoglycan levels, apoptosis and empty lacunae were compared between the three groups. The results showed a high level of deterioration in both TA and HA groups but not in the untreated group, although the thickness of cartilage in the HA group was lower compared with that in the TA and untreated groups. The proteoglycan levels in the TA group were lower compared with those in the HA group. Moreover, the number of empty lacunae in the HA group was higher compared with that in the TA group, while no difference in apoptosis was found between TA and HA groups. A significant difference was not found in the histological staining between TA and HA groups. On the other hand, a significant difference was found in cartilage deterioration between the medial and lateral sides in these groups. TA and HA groups showed comparable histological results. TA injection is cheaper and easier but has more adverse effects for patients with knee OA than HA injection. Therefore, orthopaedists should select TA or HA based on the economic and specific needs of patients.

BRAF V600E mutation in pediatric intracranial and cranial juvenile xanthogranuloma.

Juvenile xanthogranuloma (JXG) is a cutaneous form of non-Langerhans cell histiocytosis, primarily affecting children. The lesion is presumed to originate from either macrophages or dermal dendritic cells. JXG can rarely present as an isolated intracranial lesion and, in contrast to the dismal outcome of patients with systemic disease, cranial JXG has been shown to carry a more favorable prognosis. Here, we report for the first time 3 pediatric cases of JXG with a BRAF V600E mutation, 2 with intracranial lesions and 1 with cranial lesions. Although these intracranial/cranial lesions have been referred to as JXG, they likely differ from cutaneous JXG in both the clinical features and BRAF status. It may be more appropriate to classify intracranial/cranial JXG in the same group as Langerhans cell histiocytosis and Erdheim-Chester disease, which also have a BRAF V600E mutation. Further study of BRAF status in a larger series of JXG is warranted.

The temporal variations of presumptive sudden death of Thai people in Singapore and Taiwan.

BACKGROUND: Sudden Unexplained Death Syndrome (SUDS) is the major cause ofsudden death in Thai adults, especially Thai migrant workers in Singapore and Taiwan. Temporal variations of sudden death of Thai people abroad are not well known. OBJECTIVE: To study the month, day and time of death of presumptive sudden death (PSD) in Singapore, Taiwan. MATERIAL AND METHOD: The authors reviewed the death certificates of Thai people who died in Singapore and Taiwan and previously SUDS reported cases form Singapore. The time, day and month ofPSD and Non-PSD deaths in Singapore and Taiwan were compared. RESULTS: From January 1994 to January 1995, 46 SUDS died in Singapore (gr A), from May 2000 to August 2002, 39 PSD died in Singapore (gr B), from January 1999 to May 2002, 100 presumptive or probable sudden unexplained death syndrome (PSUDS) died in Taiwan (gr C) and 254 Non-PSD death aboard (gr D) as controls. The annual SUDS/PSD death rates (per 100,000) in Singapore were 91.1 in 1994, 30.7 in 2001 and 33.5 in Taiwan in 2000. All but two SUDS/PSD cases were male. The mean age in gr A + B and C were 34.9 + 7.5 and 33.1 +/- 6.0 years old respectively. In gr. A, B and C, compared with gr D, Tuesday was the weekday of lowest SUDS/PSD death rate and Saturday was the highest. (p < 0.05). Time of death in gr B and C were peak during midnight to 8 a.m. and there was some trend of seasonal variation in occurrence of SUDS/PSD with the peak death rate in April and trough death rate in September; which is significantly different from gr D (1.49% vs 10.89% of all deaths, p < 0.01). CONCLUSION: The presented data demonstrate some temporal variations in SUDS/PSD death aboard. The sudden death of Thai people in Singapore and Taiwan may be more prevalent in the "work-to-rest" than "rest-to-work" periods.